Acute Lymphoblastic Leukemia: NCCN Guidelines For Patients

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NCCN Guidelines for Patients Version 1.2016
Acute
Lymphoblastic
Leukemia
Available online at NCCN.org/patients

NCCN Guidelines for Patients Version 1.2016
Acute Lymphoblastic
Leukemia (ALL)
Learning that you have cancer can be overwhelming. The goal of this book is
to help you get the best cancer treatment. It explains which cancer tests and
treatments are recommended by experts in acute lymphoblastic leukemia. The
treatments in this book are also used for lymphoblastic lymphoma.
The National Comprehensive Cancer Network (NCCN) is a not-for-profit

alliance of 27 of the worlds leading cancer centers. Experts from NCCN have
written treatment guidelines for doctors who treat leukemias. These treatment
guidelines suggest what the best practice is for cancer care. The information in
this patient book is based on the guidelines written for doctors.
This book focuses on the treatment of acute lymphoblastic leukemia. Key

points of this book are summarized in the related NCCN Quick Guide
series for Acute Lymphoblastic Leukemia. NCCN also offers patient resources
on chronic lymphocytic leukemia, chronic myelogenous leukemia, multiple
myeloma, and other cancer types. Visit NCCN.org/patients for the full library
of patient books, summaries, and other patient and caregiver resources.
NCCN Guidelines for Patients

1
Acute Lymphoblastic Leukemia, Version 1.2016
Credits
NCCN aims to improve the care given to patients with cancer. NCCN staff work with experts to create helpful programs and
resources for many stakeholders. Stakeholders include health providers, patients, businesses, and others. One resource is the
series of books for patients called the NCCN Guidelines for Patients. Each book presents the best practice for a type of cancer.
The patient books are based on clinical practice guidelines written for cancer doctors. These guidelines are called the NCCN
Clinical Practice Guidelines in Oncology (NCCN Guidelines). Clinical practice guidelines list the best health care options for
groups of patients. Many doctors use them to help plan cancer treatment for their patients.
Panels of experts create the NCCN Guidelines. Most of the experts are from NCCN Member Institutions. Panelists may include
surgeons, radiation oncologists, medical oncologists, and patient advocates. Recommendations in the NCCN Guidelines are
based on clinical trials and the experience of the panelists. The NCCN Guidelines are updated at least once a year. When funded,
the patient books are updated to reflect the most recent version of the NCCN Guidelines for doctors. For more information about
the NCCN Guidelines, visit NCCN.org/clinical.asp.
NCCN staff involved in developing the NCCN Guidelines for Patients include:
Dorothy A. Shead, MS Lacey Marlow Susan Kidney

Director, Patient and Clinical Information Associate Medical Writer Graphic Design Specialist
Operations
Rachael Clarke
Laura J. Hanisch, PsyD Guidelines Data and Layout Coordinator
Medical Writer/Patient Information
Specialist
Endorsed by
THE Leukemia & lymphoma society (LLS)
LLS is dedicated to developing better outcomes for blood cancer patients through research, education and patient
services and is happy to have this comprehensive resource available to patients with acute lymphoblastic leukemia.
www.LLS.org/informationspecialists
Supported by NCCN Foundation
NCCN Foundation supports the mission of the National Comprehensive Cancer Network (NCCN) to
improve the care of patients with cancer. One of its aims is to raise funds to create a library of books for
patients. Learn more about the NCCN Foundation at NCCN.org/foundation.
National Comprehensive Cancer Network (NCCN)

275 Commerce Drive Suite 300
Fort Washington, PA 19034
215.690.0300
2016 National Comprehensive Cancer Network, Inc. All rights reserved.

The NCCN Guidelines for Patients and illustrations herein may not be reproduced in any form for any
purpose without the express written permission of NCCN.

2
Contents
Acute Lymphoblastic
Leukemia (ALL)
4 How to use this book 73 Part 6
Making treatment decisions
5 Part 1 Offers tips for choosing the best treatment
ALL basics for you.
Explains how and where this type of
cancer starts. 83 Glossary:
84 Dictionary
13 Part 2 90 Acronyms
Testing for ALL
Describes the tests used to confirm this 93 NCCN Panel Members
type of cancer and plan treatment.
94 NCCN Member Institutions
25 Part 3
Treatment planning 96 Index
Explains the main factors doctors use to
plan treatment thats right for you.
31 Part 4
Overview of cancer
treatments
Describes the types of treatments that are
used for ALL.
47 Part 5
Treatment guide
Presents treatment options based on your
health and age as well as the features of
the cancer.

3
How to use this book
Who should read this book? point out what applies to you and give you more
information. As you read through this book, you
Leukemia is a type of cancer that starts in may find it helpful to make a list of questions to
blood-forming cells in the bone marrow. Acute ask your doctors.
lymphoblastic leukemia is a fast-growing type of
leukemia that causes too many immature blood The recommendations in this book are based on
cells called lymphoblasts to be made in the bone science and the experience of NCCN experts.
marrow. Lymphoblastic lymphoma is similar, However, each patient is unique and these
but it causes too many lymphoblasts to build up recommendations may not be right for you. Your
in lymph nodes or other parts of the lymphatic doctors may suggest other tests or treatments
system. Patients and those who support them based on your health and other factors. If other
caregivers, family, and friendsmay find this suggestions are given, feel free to ask your
book helpful. It may help you discuss and decide treatment team questions.
with your doctors what care is best.
Making sense of medical

Where should I start terms
reading?
In this book, many medical words are included.
Starting with Part 1 may be helpful for many These are words that you will likely hear from
people. It explains what acute lymphoblastic your treatment team. Most of these words may
leukemia is. Knowing more about this cancer be new to you, and it may be a lot to learn.
may help you better understand its treatment.
Parts 2 and 3 explain how doctors assess for Dont be discouraged as you read. Keep reading
this type of cancer and plan treatment. Part and review the information. Be sure to ask your
4 briefly describes all the types of treatment. treatment team to explain a word or phrase that
Part 5 is a guide to which treatment options you dont understand.
are recommended for you. Part 6 offers some
helpful tips for anyone making treatment Words that you may not know are defined in the
decisions. text or in the Dictionary. Words in the Dictionary
are underlined when first used on a page.
Acronyms are defined in the text when first used
and are also defined in the Glossary. Acronyms
Does the whole book apply are words formed from the first letters of other
to me? words. One example is CBC for complete blood
count.
This book includes information for many
situations. Thus, you will likely not get every test
and treatment listed. Your treatment team can

4
1
ALL basics

5
1 ALL basics
6 What are lymphoblasts?
8 What is ALL?
10 What are the symptoms of ALL?
12 Review
What are lymphoblasts?

Youve learned that you have or may
Blood is made of many types of cells. The three main
have ALL. Part 1 explains some types are platelets, red blood cells, and white blood
basics about this cancer that may cells. Each type of blood cell has a different job.
Platelets help control bleeding. Red blood cells carry
help you learn about it and start to
oxygen throughout the body. White blood cells help
cope. These basics may also help you fight germs and infections in the body. They are part
start planning for treatment. of your bodys disease-fighting systemcalled the
immune system.
Lymphoblasts are a type of very young white blood

cells. Over time, they become mature white blood
cells called lymphocytes. Lymphocytes are mostly
found in the blood and lymphatic system.
The two main types of lymphocytes are

B-lymphocytes (B-cells) and T-lymphocytes (T-cells).
B-cells make antibodies that mark germs for killing.
T-cells alert your body that germs are present, kill
diseased cells, and help B-cells work.
Most blood cells are made in the bone marrow. Bone

marrow is the soft, sponge-like tissue in the center

6
1 ALL basics What are lymphoblasts?
of most bones. See Figure 1.1. Blood cells are See Figure 1.2. Blast cells are new, very young
made from special blood-forming cells called blood (immature) blood cells that grow into adult (mature)
stem cells. Blood stem cells can become any type of blood cells over time. Different types of blast cells
mature blood cell. become different types of mature blood cells. Once
they are mature, the blood cells leave the bone
Blood stem cells go through a series of changes as marrow and enter the bloodstream.
they grow and develop to make new blood cells.
Figure 1.1
Blood cells in bone marrow
Bone marrow is the soft, sponge-like

tissue in the center of most bones.
Blood stem cells in the bone marrow
make all types of blood cells.
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
Blood stem cell
Figure 1.2
Blood stem cells make all types of
blood cells
A blood stem cell goes through

many steps to become a red blood
cell, white blood cell, or platelet.
Blast cells are very young blood
cells that grow into mature blood
cells over time. Lymphoblasts grow B-cell T-cell
Red blood Platelets Granulocytes
into mature white blood cells called cells
lymphocytes. White blood cells
help protect the body from infection
and disease. Plasma cell

7
1 ALL basics What is ALL?
What is ALL? Normal blood cells grow and then divide to make new
red blood cells, white blood cells, and platelets as the
Leukemias are cancers that start in blood-forming body needs them. When normal blood cells grow old
cells in the bone marrow. There is more than one type or get damaged, they die. New blood cells are then
of leukemia. Each type of leukemia is named based made to replace the old ones. In a person with ALL,
on how fast it grows and the type of blood cell in too many lymphoblasts are made.
which it begins.
Inside of all cells are coded instructions for building
This book focuses on ALL (acute lymphoblastic new cells and controlling how cells behave. These
leukemia). Acute means the leukemia grows and instructions are called genes. Genes are a part
progresses very fast. Lymphoblastic means it starts of DNA (deoxyribonucleic acid). DNA is grouped
in young white blood cells called lymphoblasts. together into long strands called chromosomes.
Lymphoblastic lymphoma is similar to ALL. The main See Figure 1.3. Changes (mutations) in genes
difference is that it starts in lymphoblasts within the cause normal lymphoblasts to become cancer cells.
lymphatic system. Researchers are still trying to learn what causes
genes to change and cause cancer.
Figure 1.3 Human

Chromosomes and genes in cells cell
Genes are coded instructions in cells

for making new cells and controlling
how cells behave. Genes are a
part of DNA, which is bundled into
long strands called chromosomes.
Every normal cell has 23 pairs of
chromosomes.
Gene
Chromosomes
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved.

www.nucleusinc.com

8
1 ALL basics What is ALL?
The abnormal lymphoblasts are called leukemia cells. Third, leukemia cells can spill out of the bone marrow
Leukemia cells differ from normal cells in a few key into the bloodstream. They can then spread to other
ways. First, leukemia cells grow more quickly and parts of the body. They may collect in the spleen,
live longer than normal cells. They divide and copy thymus, lymph nodes, liver, testicles, and the area
themselves to make more and more leukemia cells. around the brain and spinal cord.
See Figure 1.4. The leukemia cells quickly fill up the
bone marrow and crowd out healthy blood cells that
body needs.
Second, leukemia cells dont grow into mature

lymphocytes the way they should. They stay as young
blast cells that dont work well. They dont help fight
infections in the body.
Figure 1.4
Normal cell growth versus leukemia
cell growth
Normal cells grow and divide to make

new cells as the body needs them.
Normal cells die when they are old or
damaged. New cells are then made to
replace the old. Leukemia cells dont
die when they should. Instead, they
continue to grow and divide to make
more and more copies of themselves.
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved.

www.nucleusinc.com

9
1 ALL basics What are the symptoms of ALL?
What are the symptoms of ALL?

A symptom is a health problem a person experiences
that may indicate a disease. ALL can cause a number
of different symptoms. But, some people with ALL
may have few or no symptoms. Symptoms may
result from a shortage of healthy blood cells or from
leukemia cells collecting in certain parts of the body.
Some common symptoms that may be caused by ALL

include:
Severe tiredness (fatigue),

Weakness,
Dizziness,
Shortness of breath,
Frequent infections,
Fever,
Bruising or bleeding easily,
Pain in arms, legs, or joints,
Unusual sweating at night,
Unexplained weight loss, and
Feeling of fullness in the belly area beneath
the ribs.
However, these symptoms may be caused by other

health conditions.

10
1 ALL basics Notes
My notes

11
1 ALL basics Review
Review
White blood cells are part of your bodys Leukemia is a cancer that starts in blood-
disease-fighting system called the immune forming cells in the bone marrow.
system.
ALL is a fast-growing type of leukemia in
Most blood cells are made in the bone which too many young white blood cells called
marrowthe soft tissue in the center of most lymphoblasts are made. The lymphoblasts
bones. build up in the bone marrow and crowd out
healthy blood cells.
All types of blood cells are made from special
blood-forming cells called blood stem cells. Lymphoblastic lymphoma is similar to ALL.
The key way it differs is that it starts in
Blast cells are very young (immature) cells
lymphoblasts within the lymphatic system.
that become mature blood cells over time.

12
2
Testing for ALL

13
2 Testing for ALL
14 Medical history
16 Physical exam
16 Blood tests
18 Bone marrow tests
20 Genetic tests
22 Spinal fluid test
23 Imaging tests
24 Review
Medical history
Treatment planning starts with testing.
Your medical history includes any health events in
This section describes the tests that your life and any medicines youve taken. You will
are used to confirm (diagnose) ALL be asked about any illnesses, injuries, and health
problems youve had. Some health problems run in
and plan treatment. This information
families. Thus, your doctor may also ask about the
can help you use the Treatment guide health of your blood relatives.
in Part 5. It may also help you know
ALL may cause symptoms. Its important that your
what to expect during testing. Not doctor knows if you have them. Symptoms may
every person with acute lymphoblastic result from a shortage of blood cells. Or, they may
result from leukemia cells collecting in certain parts
leukemia will receive every test listed.
of the body. But, some patients may have few or no
symptoms of ALL.
A medical history is needed for treatment planning.

See Chart 2.1 and Chart 2.2 for a full list of the tests
that may be recommended before treatment for ALL.
It may help to make a list of old and current medicines
while at home to bring to your doctors office.

14
2 Testing for ALL Medical history
Chart 2.1 Initial tests for diagnosis
Tests of blood or bone marrow needed for all patients
Cell assessment (morphologic assessment)

Cytogenetic testing
Flow cytometry
FISH (fluorescence in situ hybridization)
PCR (polymerase chain reaction)
Chart 2.2 Tests for treatment planning
Tests needed for all patients Tests that may be needed in some cases
Medical history and physical exam MRI (magnetic resonance imaging) of the head
CBC (complete blood count) with differential CT (computed tomography) of the head
Blood chemistry profile CT of the chest
TLS (tumor lysis syndrome) panel PET (positron emission tomography) of the chest
Blood clotting tests Echocardiogram
Lumbar puncture HLA (human leukocyte antigen) typing

15
2 Testing for ALL Physical exam | Blood tests
Physical exam Blood tests

Doctors usually perform a physical exam along with Doctors test blood to look for signs of disease and to
taking a medical history. A physical exam is a review check your general health. Blood tests are done along
of your body for signs of disease such as infection with other initial tests to help confirm ALL. Blood
and areas of unusual bleeding or bruising. tests may be repeated to check how well treatment
is working and to check for side effects. For a blood
Your doctor may listen to your lungs, heart, and test, your doctor will insert a needle into a vein to
intestines. Your doctor may also feel different parts of remove a sample of blood. The blood sample will then
your body to see if organs are of normal size, are soft be sent to a lab for testing. At the lab, a pathologist
or hard, or cause pain when touched. For example, will examine the blood with a microscope and perform
your doctor may feel your belly area (abdomen) to other tests.
check for signs of an enlarged liver or spleen. In
males, the testicles will also be examined. CBC with differential
A CBC (complete blood count) is a test that measures
Checking for signs of infection is a key part of the the number of blood cells in a blood sample. It
physical exam. This is often referred to as an infection includes the number of white blood cells, red blood
evaluation. Enlarged lymph nodes are an example cells, and platelets. The CBC includes a differential
of a common sign of infection. Your doctor may feel count. The differential measures the different types of
certain areas such as your armpits and behind your white blood cells in the sample.
jaw to check for enlarged lymph nodes.
A high number of white blood cells and a low number
of red blood cells and platelets may be signs of ALL.
This is because ALL causes too many young white
blood cells to be made. These white blood cells may
crowd the bone marrow so that too few normal blood
cells are made.
A CBC with differential is given with other initial tests

when ALL is first suspected. It is not used alone to

16
2 Testing for ALL Blood tests
diagnose ALL, but it can tell your doctor about your dangerous. It can cause serious damage to organs
overall health. This test is also repeated to check such as the kidneys and heart.
treatment results.
Blood clotting tests
Blood chemistry profile Blood clotting tests are used to assess if blood is able
A blood chemistry profile measures the levels of to clot (coagulate) the way it should. Platelets and
different chemicals in your blood. Chemicals in your proteins called clotting factors help control bleeding in
blood come from you liver, bone, and other organs the body.
and tissues. Abnormal levels of certain chemicals in
the blood may be a sign that an organ isnt working When a person is cut or injured, platelets and clotting
well. Abnormal levels can be caused by cancer or factors clump together to form a clot to stop bleeding.
other health problems. Abnormal levels of platelets or clotting factors can
cause bleeding problems.
A blood chemistry profile is given along with other
initial tests for ALL. Doctors use this test to assess the HLA typing
general health of your body and organs. It can help HLAs (human leukocyte antigens) are special
check for organ damage caused by the leukemia cells proteins found on the surface of most cells in the
or ALL treatments. body. The unique set of HLA proteins on a persons
cells is called the HLA type or tissue type. All cells
Liver function tests in a single person have the same HLA type. This
The liver is an organ that removes waste from the helps the body to tell its own cells apart from foreign
blood and helps to digest food. Liver function tests cells. It also affects how the body responds to foreign
may be done along with a blood chemistry profile. substances.
This is to check the health of your liver.
HLA typing is a blood test that finds a persons
Liver function tests measure chemicals that are made HLA type. This test is used to find the right donor
or processed by the liver. Abnormal levelstoo low or for a stem cell transplanta treatment that may be
too highmay be a sign that your liver isnt working considered for some patients with ALL. (See Part 4 on
well. Abnormal levels may be caused by cancer, page 42 for details about this treatment). Your tissue
cancer treatments, or other health problems. type and the donors tissue type must be a near-
perfect match for this treatment to work.
Tumor lysis syndrome panel
TLS (tumor lysis syndrome) is a condition that Type and screen
occurs when many cancer cells die very quickly due Blood types differ among people just like tissue types
to treatment. As cancer cells die, they release their differ among people. Type and screen is test that
contents into the blood. This can cause very high finds a persons blood type. It also looks for signs that
levels of certain chemicals in the blood. certain blood types may not be a good match or may
not be safe to give to a patient. This test is needed if
A TLS panel measures the levels of these chemicals you will receive a transfusion of blood from another
in the blood. Uric acid is one of the chemicals person (donor). The donors blood type must be a
released by dying cancer cells. Very high levels of good match that works well with your blood type.
uric acid and other chemicals in the blood can be very

17
2 Testing for ALL Bone marrow tests
Bone marrow tests local anesthesia to numb the area of skin and
bone beneath. Once numb, a hollow needle will be
Bone marrow biopsy and aspiration inserted into your skin and then pushed into the bone
To confirm if you have ALL, a sample of tissue must to remove the liquid bone marrow with a syringe.
be removed from your body for testing. This tissue Then, a wider needle will be inserted into the bone
might be a blood sample, a biopsy of an enlarged to remove the solid bone and marrow sample. You
lymph node or organ, or a sample of bone marrow. may feel some pain while the samples are being
removed. Your skin may be bruised for a few days.
A bone marrow biopsy removes a small piece of solid The samples will be sent to a lab for testing.
bone along with a small amount of soft bone marrow
inside the bone. A bone marrow aspiration removes Cell assessment
a small amount of liquid bone marrow from inside the At the lab, a pathologist will look at the cells in a blood
bone. Often, both tests are done at the same time or bone marrow sample with a microscope. This
on the back of the hip bone. You will likely lie on your test is simply called cell assessment. Doctors may
side during this test. See Figure 2.1. also refer to this test as a morphologic assessment.
Special dyes may be used to stain the sample. This
You may be given a light sedative before the test. helps to show the differences between parts of a
Your doctor will then clean the area of skin where single cell and between many cells.
the biopsy will be done. Next, you will receive
Figure 2.1
Bone marrow biopsy
Doctors use a bone marrow

biopsy and aspiration to
remove a sample of bone
marrow for testing. These tests
are often done at the same
time on the hip bone.

18
2 Testing for ALL Bone marrow tests
The pathologist will look at the size, shape, type, the number of leukemia cells present. This is helpful
and other features of the cells in the blood or bone for checking treatment results.
marrow sample. This is to see if the cells look more
like normal, mature cells or more like abnormal, Flow cytometry is sometimes used to measure the
immature cells. The number of very immature cells amount of DNA in the leukemia cells. In such cases,
blast cellsin the sample is important. a marker that reacts with DNA is used. The amount of
DNA reflects the number of chromosomes in the cells.
Normally, there are no blast cells in the blood. And, in This can help to show if the cells have too many or
a healthy person, blast cells make up no more than too few chromosomes.
5% of cells in the bone marrow. This means that no
more than 5 out of every 100 cells in the bone marrow
are blast cells. In a person with ALL, blast cells make
up 25% or more of cells in the bone marrow. This
means that at least 25 out of every 100 cells are blast
cells.
Flow cytometry
Flow cytometry is used to identify and count types
of cells in a sample. It can show if cells are normal
or abnormal. It can also tell the difference between
types of leukemia cells. This test is used to help
confirm ALL and find out the type of lymphocytes in
which it started. Flow cytometry is also used to check
treatment results.
ALL cells have a common pattern or signature of

proteins. The type and pattern of proteins differs
based on the type of maturity of the cell. The pattern
of surface proteins is called the immunophenotype.
Flow cytometry can identify the type of leukemia cells

present based on the pattern of surface proteins.
This is called immunophenotyping. A sample of bone
marrow is often used for immunophenotyping, but a
blood sample may also be used.
Flow cytometry involves first adding a markera

light-sensitive dyeto cells. The marker reacts with
surface proteins found only on certain types of cells.
The cells are then passed through a flow cytometry
machine. The machine identifies leukemia cells based
on the pattern of surface proteins. It can also count

19
2 Testing for ALL Genetic tests
Genetic tests chromosomes. This test can also be used to count

the number of leukemia cells.
Cytogenetic testing
Cytogenetic testing uses a microscope to examine the Many types of chromosome changes can happen
chromosomes inside cells. This type of test is used to in ALL. The leukemia cells may have an abnormal
look for abnormal changes in the chromosomes of the number of chromosomestoo many or too few. The
leukemia cells. It is often done on a sample of bone leukemia cells may also have more than one type of
marrow. It can also be done on a sample of blood. chromosome change.
Certain chromosome changes in the leukemia cells Sometimes parts of chromosomes break off and
can affect treatment options and outlook. Thus, this is switch with each other. This is called a translocation.
a key test that is used to help plan treatment for ALL. The Philadelphia chromosome is a key example of
This test is given along with other initial tests when a translocation that happens in some people with
ALL is first diagnosed. It may also be repeated to ALL. The Philadelphia chromosome is caused by a
check treatment results. translocation between parts of chromosomes 9 and
22. See Figure 2.2.
Fort this test, a pathologist will look at a map of the
chromosomes under a microscope. This map is called This translocation also forms the abnormal BCR-
a karyotype. It will show if there are any abnormal ABL fusion gene on the Philadelphia chromosome. A
changes in the size, shape, structure, or number of fusion gene is a new gene that is formed when parts
of two separate genes are joined (fused) together.
Figure 2.2
Philadelphia chromosome
The Philadelphia
chromosome is formed by a
translocation between parts
of chromosomes 9 and 22.
It contains the abnormal
BCR-ABL fusion gene.
This is a key chromosome
change that affects which
treatments are best for you.

20
2 Testing for ALL Genetic tests
FISH PCR/MRD
FISH (fluorescence in situ hybridization) is a very PCR (polymerase chain reaction) is a very sensitive
sensitive lab test that can detect certain abnormal test. Like FISH, it detects abnormal gene and
changes in a cells genes or chromosomes. It can chromosome changes (mutations) in cells. However,
detect most abnormal changes that can be seen with it can find mutations that are too small to be seen with
a microscope. It can also detect some changes that a microscope.
are too small to be seen with basic cytogenetic testing
(karyotyping). Doctors use this test to detect certain gene and
chromosome changes that are commonly found in
Doctors use FISH to detect certain abnormal gene ALL. An example of this is the BCR-ABL fusion gene.
and chromosome changes in leukemia cells. This This gene is found on the Philadelphia chromosome.
test uses special color dyes, called probes, that PCR can detect gene mutations and measure the
attach only to certain genes or parts of certain number of cells that have them.
chromosomes.
PCR is very helpful for checking how well treatment
For example, the Philadelphia chromosome is a is working. When the cells have certain genetic
common abnormal change found in adults with ALL. changes, PCR can find and measure the amount of
This chromosome contains the BCR-ABL fusion leukemia cells left. This test can find one leukemia
gene. To detect this, FISH uses color probes that cell among more than 10,000 normal cells. PCR
attach to the BCR gene and the ABL gene. The BCR- is the method used to find the amount of disease
ABL fusion gene is shown by the overlapping colors present after treatment. Doctors use this to assess
of the two probes. for MRD (minimal residual disease). The presence of
MRD is a key factor used to decide if more treatment
Like cytogenetic testing, FISH is used to help plan is needed. (See page 39 for more details about
and monitor treatment for ALL. This test can be checking treatment results.)
performed on a sample of blood or bone marrow.
PCR can be done on a sample of bone marrow or
blood. But, bone marrow is often preferred, especially
when checking treatment results.

21
2 Testing for ALL Spinal fluid test
Spinal fluid test During this test, you will be lying down or sitting on
an exam table as shown in Figure 2.3. If lying down,
ALL can spread to the fluid around your brain and your knees will be tucked up near your chest. If
spinal cord. This is called cerebrospinal fluid or spinal sitting, you will lean slightly forward and down over
fluid. To determine whether or not cancer is in spinal your knees.
fluid, a sample must be removed and tested.
Local anesthesia will be used to numb the lower part
A lumbar puncture is a procedure that is used to of your back over your spine. Next, a thin needle will
remove spinal fluid. It is also called a spinal tap. be inserted between the bones of your spine and
A lumbar puncture is often done when ALL is first into the space around your spinal cord. The needle
diagnosed. But, it may be done at a later time that fits will be used to take a sample of spinal fluid. You may
with your treatment plan. A lumbar puncture can also feel some pressure during the procedure. The fluid
be used to inject cancer drugs into the spinal fluid. sample will then be sent to a lab for testing for the
presence of leukemia cells.
Figure 2.3
Lumbar puncture
Doctors perform a lumbar

puncture to remove a sample of
spinal fluid to test for leukemia
cells. A lumbar puncture may
also be used to give liquids
such as drug treatments.
When drugs are injected into
the spinal fluid, it is called IT
(intrathecal) therapy.

22
2 Testing for ALL Imaging tests
Imaging tests PET is not a standard test for ALL and it is not needed
for all patients. But, a PET scan of your chest is
Imaging tests take pictures of the inside of your body. recommended if other tests showed a mass in your
Imaging tests are not often used for ALL. However, chest. It may be done again after treatment to check if
they may be useful to look for infections or to check for the mass in your chest is gone.
signs that ALL has spread to the brain and spinal cord.
Echocardiogram
Imaging tests are often easy to undergo. Before the An echocardiogram is an imaging test of your heart. It
test, you may be asked to stop eating or drinking for uses sound waves to make pictures. This test is used
several hours. You also should remove any metal to check how well your heart is working. It shows your
objects that are on your body. For some imaging doctor how your heart is beating and pumping blood.
tests, a contrast dye may be injected into your vein to
make the pictures clearer. Some treatments for ALL can damage your heart.
Thus, your doctor may want to test how well your
CT scan heart works to plan treatment. This is especially
CT (computed tomography) takes many pictures of important if youve had any heart problems in the
a body part from different angles using x-rays. See past. This test may be repeated during and after ALL
Figure 2.4. A computer combines all the pictures to treatment to check for any heart damage that may
make one clear picture. A CT scan of your head may have occurred.
be needed if you have symptoms that suggest ALL
might have spread to your brain and spinal cord. A CT
Figure 2.4 CT scan machine
scan of your chest may be needed for certain patients
to see if leukemia cells have collected in this area. A CT machine is large and has a tunnel in the
middle. During the test, you will lie on a table
that moves slowly through the tunnel.
MRI scan
MRI (magnetic resonance imaging) uses radio waves
and magnets to take pictures of the inside the body.
MRI scans create clear pictures of soft tissues and
bones. MRI scans are also very helpful for looking at
the brain and spinal cord. An MRI scan of your head
should be done if you have symptoms that suggest
ALL might have spread to your brain and spinal cord.
PET scan
PET (positron emission tomography) shows how your
cells are using a simple form of sugar. For a PET
scan, a sugar radiotracer will first be injected into your
body. The radiotracer is detected by a special camera
during the scan. Cancer cells look brighter than
normal cells because they use sugar more quickly.

23
3
2 Testing
DCIS for ALL Genetic
Review
counseling | Treatment
Review
Cancer tests are used to plan treatment and Flow cytometry is used to identify the type of
check how well treatment is working. cells present in a sample based on the set
on proteins on the cell surface. This is called
Your medical history and the physical exam
immunophenotyping.
can reveal signs of disease.
Cytogenetic testing, PCR, and FISH help
Blood tests are used to look for signs of
doctors detect abnormal chromosome
cancer and check how well your organs are
changes in leukemia cells.
working.
To confirm if you have ALL, a sample of

tissueblood or bone marrowmust be
removed from your body for testing. A bone
marrow biopsy and aspiration are used to
remove a sample of bone marrow.

24
3
Treatment Planning

25
3 Treatment Planning
27 Subtypes of ALL
28 Age issues in ALL
29 What is a prognostic factor?
30 Review
Doctors look at a number of factors to

plan the best treatment for you. This
includes your age, general health, and
certain features of the leukemia cells.
Some of these factors can also affect
and help predict the likely treatment
outcome (prognosis). Part 3 describes
each of these factors and how they
are used to plan treatment.

26
3 Treatment Planning Subtypes of ALL
Subtypes of ALL Cytogenetic subtypes

Doctors also group ALL into subtypes based on the
ALL is divided (classified) into smaller groups based on type of abnormal changes found in the chromosomes
certain features of the leukemia cells. These smaller of the leukemia cells. Cytogenetics is the study of
groups are called subtypes. The ALL subtype is an chromosomes. Thus, ALL subtypes that are based on
important factor that doctors use to plan treatment. chromosome changes are called cytogenetic subtypes.
Cell subtypes Many types of chromosome changes may happen

Doctors classify ALL into two broad subtypes based in ALL. The Philadelphia chromosome is an
on the type of lymphocyte the leukemia cells come abnormal chromosome found in the leukemia cells
from. These are called cell subtypes. Each type of of some people with ALL. It is formed when parts of
lymphocyte can be identified by the unique set of chromosomes 9 and 22 break off and switch with each
proteins on the surface of the cells. The unique set and other.
pattern of proteins is called the immunophenotype.
ALL can be grouped into many subtypes based on
There are many ALL cell subtypes based on chromosome changes. Some are more common or
immunophenotype. Some are more common or more more important for treatment planning than others. The
important for treatment planning than others. The two two main cytogenetic subtypes that doctors use for
main cell subtypes based on immunophenotype are treatment planning are described next.
described below.
Ph-positive ALL In this subtype of ALL,
B-cell ALL This subtype of ALL starts in the leukemia cells have the Philadelphia
young cells that normally become mature chromosome. This is the most common
B-cells (B-lymphocytes). This is the most cytogenetic subtype in adults with ALL. It is
common ALL subtype overall. Among adults rare in children. The chance of having this
with ALL, about 75 out of 100 have B-cell ALL. cytogenetic subtype increases with age.
Among children with ALL, about 88 out of 100 Among adults with ALL, about 25 out of 100
have this subtype. have Ph-positive ALL. Among children with
T-cell ALL This subtype of ALL starts in ALL, about 3 out of 100 have this subtype.
young cells that normally become mature Ph-negative ALL In this subtype of
T-cells (T-lymphocytes). This subtype is less ALL, the leukemia cells do not have the
common overall, but occurs more often in Philadelphia chromosome. This cytogenetic
adults than in children. Among adults with subtype is more common in children than in
ALL, about 25 out of 100 have T-cell ALL. adults. Among adults with ALL, about 75 out
Among children with ALL, about 12 out of 100 of 100 have Ph-negative ALL. Among children
have this subtype. with ALL, more than 95 out of 100 have this
subtype.

27
3 Treatment Planning Age issues in ALL
Age issues in ALL results. The side effects of intensive treatments tend
to be more severe and harder to recover from for
A persons age at the time ALL is diagnosed is one older patients.
of the most important factors that doctors use to
plan treatment. As a result, recommendations in the Generally, doctors use the age of 65 as the cut-off for
Treatment guide are divided into two age groups: intensive treatments. This is because older patients
may not be able to tolerate them. But, age alone is
AYAs (adolescent and young adults) not a good gauge for deciding if a person can tolerate
patients who are 15 to 39 years of age, and these treatments.
Older adults patients who are 40 years of
age or older. A person older than 65 may be still in good health
overall and not have other serious health problems.
AYAs and older adults differ in many ways. These In this case, he or she may still benefit from more
differences carry over into personal, social, emotional, intensive treatments. Likewise, a person younger than
and medical needs. There are also key differences 65 may be in poorer health overall and have other
between AYAs and older adults with ALL that doctors serious health problems. In this case, he or she may
must consider when making treatment decisions. In not be able to tolerate intensive treatments.
particular, AYAs have much better outcomes when
given more intensive ALL treatments like those Thus, doctors must also consider your overall health
designed for children. as well as your age. Assessing your overall health,
fitness, and other current health problems is very
Intense treatments can cause serious side effects important. This includes checking how well organs
that get harder to tolerate with age. Because AYAs such as your heart, lungs, liver, and kidneys are
are usually able to tolerate the intensive treatments, working.
they benefit greatly and have much better treatment
AYAs have a unique set of needs and

challenges that differ greatly from
those of young children and older
adults.
Discussing all of these important aspects is

beyond the scope of this book. More details and
information focused on AYAs with cancer can
be found in the NCCN Guidelines for Patients:
Caring for Adolescents and Young Adults. These
guidelines are available for free at
www.nccn.org/patients.

28
3 Treatment Planning What is a prognostic factor?
What is a prognostic factor? Age: The leukemia cells in older patients tend to be
more resistant to treatment. Stronger treatments may
Several important factors affect treatment options be needed to kill all the leukemia cells and keep them
and the likely outcome (prognosis) of ALL. Something from coming back.
that affects and helps predict prognosis is called a
prognostic factor. Philadelphia chromosome: Leukemia cells that
have the Philadelphia chromosome can be harder to
Doctors use certain prognostic factors to help predict treat. But, new treatments have improved outcomes
how ALL will likely progress and respond to treatment. in the past few years.
This helps doctors plan how intensive treatment
needs to be for each patient to kill all the leukemia Chromosome changes: Certain changes in
cells and keep them from coming back. These factors chromosomes can make leukemia cells harder to
can also help doctors decide which type of treatment treat. This includes having fewer than the normal
will likely work best. number of chromosomes and having five or more
chromosome changes in the leukemia cells.
Some prognostic factors are linked with a lower
chance (risk) that ALL will come back after treatment. White blood cell count: The number of white
These are called good risk features. Other factors blood cells in the blood at the time ALL is diagnosed
are linked with a higher risk that ALL will come back can also affect prognosis. Having a very high white
after treatment. These are called poor risk features. blood cell count at diagnosis is a poor risk feature in
children and adolescents with ALL. This factor has a
Doctors give more intensive treatments for ALL that much smaller effect on treatment planning for adults
has poor risk features. But, the presence of poor risk with ALL.
features does not mean ALL cant be cured.

A number of factors can affect prognosis in ALL.
Some are more important for treatment planning
than others. The two main factors doctors use to plan
treatment are your age and the cytogenetic subtype.
But, other prognostic factors for ALL that may also be
helpful include:

29
3 Treatment Planning Review
Review
A number of factors help guide treatment ALL is classified into groups based on the
options and the likely outcome (prognosis). type of cellcalled the cell subtype. It is also
classified into smaller groups based on the
Something that affects and helps predict the
type of chromosome changes in the leukemia
likely outcome is called a prognostic factor.
cells. These are called cytogenetic subtypes.
Age is one of the most important factors that
affect treatment options.
To help plan treatment, ALL is classified into

smaller groups called subtypes based on
certain features of the leukemia cells.

30
4
Overview of cancer treatments

31
4 Overview of cancer
treatments
33 Clinical trials
34 Chemotherapy
40 Targeted therapy
42 Stem cell transplant
44 Radiation therapy
45 Supportive care
46 Review
Part 4 describes the main treatments

that are used for ALL. Knowing what a
treatment is will help you understand
your treatment options listed in the
Treatment guide in Part 5. There is
more than one treatment for ALL. Not
every person with ALL will receive
every treatment listed in this chapter.

32
4 Overview of cancer treatments Clinical trials
Clinical trials Phase IV trials test new drugs approved by the

FDA (U.S. Food and Drug Administration) in many
Clinical trials are a very important treatment option patients with different types of cancer.
for ALL. New tests and treatments arent offered to
the public as soon as theyre made. They first need Joining a clinical trial has benefits. First, youll have
to be studied. A clinical trial is a type of research that access to the most current cancer care. Second, you
studies a test or treatment. will receive the best management of care. Third, the
results of your treatmentboth good and badwill be
Clinical trials study how safe and helpful tests and carefully tracked. Fourth, you may help other people
treatments are. When found to be safe and helpful, who will have cancer in the future.
they may become tomorrows standard of care.
Because of clinical trials, the tests and treatments in Clinical trials have risks, too. Like any other test or
this book are now widely used to help people with treatment, there may be side effects. Also, new tests
ALL. Future tests and treatments that may have or treatments may not help. Another downside may
better results than todays treatments will depend on be that paperwork or more trips to the hospital are
clinical trials. needed.
Clinical trials are an important treatment option To join a clinical trial, you must meet the conditions
for people with ALL. Doctors are still studying of the study. Patients in a clinical trial often have a
what treatments work best for ALL. NCCN experts similar cancer type and general health. This is to
recommend that all patients with ALL receive know that any progress is because of the treatment
treatment on a clinical trial if possible. Receiving and not because of differences between patients.
treatment on a clinical trial has been shown to
improve outcomes. To join, youll need to review and sign a paper called
an informed consent form. This form describes the
New tests and treatments go through a series of study in detail. The studys risks and benefits should
clinical trials to make sure theyre safe and work. be described and may include others than those
Without clinical trials, there is no way to know if a test described above.
or treatment is safe or helpful. Clinical trials are done
in four steps, called phases. Some examples of the Ask your treatment team if there is an open clinical
four phases of clinical trials for treatment are: trial that you can join. There may be clinical trials
where you are getting treatment or at other treatment
Phase I trials aim to find the best dose and way centers nearby. You can also find clinical trials
to give a new drug with the fewest side effects. through the websites listed in Part 6.
Phase II trials assess if a drug works to treat a

specific type of cancer.
Phase III trials compare a new drug to the

standard treatment.

33
4 Overview of cancer treatments Chemotherapy
Chemotherapy Corticosteroids, also simply called steroids, are often

given along with chemotherapy drugs to treat ALL.
The main treatment for ALL involves the long-term Steroids are drugs that are used to relieve swelling
use of chemotherapy. Chemotherapy is the use and inflammation. But, some steroids also have anti-
of drugs to kill cancer. Many people refer to this cancer effects. The two main steroids used in ALL
treatment as chemo. Chemotherapy drugs kill regimens prednisone and dexamethasone.
fast-growing cells throughout the body,
including normal cells and cancer cells.
Different types of chemotherapy drugs

Chart 4.1 Common chemotherapy drugs for ALL
work different ways to kill leukemia cells
or stop new ones from being made. Thus,
Generic name Brand name (sold as)
more than one drug is often used. When
only one drug is used, its called a single 6-MP (6-mercaptopurine) Purinethol, Purixan
agent. A combination regimen is the use
Asparaginase erwinia
of two or more cancer drugs. This is also Erwinaze
chrysanthemi
called multiagent chemotherapy.
Clofarabine Clolar
Chemotherapy is given in cycles of Cyclophosphamide Cytoxan
treatment days followed by days of rest.
This allows the body to recover before the Cytarabine Cytosar-U
next treatment cycle. Cycles vary in length Daunorubicin Cerubidine
depending on which drugs are used. The
number of treatment days per cycle and Dexamethasone --
the total number of cycles given also varies Doxorubicin Adriamycin
based on the regimen used.
Etoposide, Etoposide Etopophos
phosphate Preservative Free
A regimen is a treatment plan that specifies
the drug(s), dose, and schedule for a Idarubicin Idamycin
course of treatment. A chemotherapy
Ifosfamide Ifex
regimen consists of a set number of
cycles given over a set amount of time. Methotrexate Folex, Mexate
You may be given one drug at a time or Nelarabine Arranon
combinations of drugs at the same time.
Pegaspargase Oncaspar
Treatment for ALL often uses 4- or 5-drug Prednisone --
combination regimens. Some of the most
common chemotherapy drugs used for ALL Vincristine Oncovin
are listed in Chart 4.1. VSLI (vincristine sulfate
Marqibo
liposome injection)

34
How chemotherapy drugs are given vein in your chest or upper arm. The other end of the
Chemotherapy drugs may be given as a pill that you central line may stay outside of your body. Or, it may
swallow or as a liquid that is injected into your body be attached to a port that is placed just under your
with a needle. When given this way, the drugs travel skin. See Figure 4.1.
in your bloodstream to kill leukemia cells in all parts of
your body. This is called systemic chemotherapy. With a central line, doctors can give IV chemo
treatments without sticking your vein with a needle
Drugs may be injected into a vein, muscle, or under every time. Doctors can also use the central line
your skin. An IV (intravenous) infusion is a slow to give other medicines and take blood samples. A
injection into a vein. The IV infusion may take a few central line can be left in place for weeks or months.
hours. Or, it may be given over several dayscalled
a continuous infusion. An intramuscular injection is Leukemia cells can also spread to the brain
when drugs are given into a muscle. A subcutaneous and spinal cord. This is called CNS disease.
injection is when drugs are given under the skin. Chemotherapy that is injected into a vein cannot
always reach this area. Instead, drugs must be
Often, doctors give IV chemotherapy through a thin, injected directly into the spinal fluid. When drugs are
soft tube called a central venous line or catheter. One given this way, it is called IT (intrathecal) therapy or IT
end of the central line will be inserted into a large chemotherapy. IT chemotherapy is often given during
Figure 4.1
Central venous line and port
Chemotherapy is often given

as a slow injection into a vein
through a long, thin tube. This
tube is called a central venous
line or catheter. The central line
may be attached to a port that is
placed just under your skin.

35
a lumbar puncture. (See Figure 2.3 on page 22.) to adults. Some patients may develop an allergy to
IT chemotherapy is used to prevent and treat CNS pegaspargase. If this happens, asparaginase erwinia
disease. chrysanthemi may be given instead.
Regimens for AYAs and older adults In contrast, adult regimens tend to use more
A protocol is a detailed outline or plan of a medical cyclophosphamide and anthracyclines such
treatment, study, or procedure. A treatment protocol as doxorubicin and daunorubicin. These drugs
covers all phases of ALL treatment. It states which lower (suppress) the bone marrows ability to
drugs and regimens will be used during each make new blood cells. Thus, they are also called
phase of treatment. A protocol often includes many myelosuppressive drugs. Adult regimens also use
chemotherapy regimens that are given at different allogeneic SCT (stem cell transplant) more often.
times over the course of ALL treatment. (See page 42 for details on this type of treatment.)
Treatments designed for children with ALL are called Dose intensification: Intensified doses of drugs
pediatric protocols. The chemotherapy regimens are given at certain points during treatment for
used for children are often called pediatric regimens. children and adults. But, pediatric protocols give
Likewise, treatments designed for older adults with intensified doses more often throughout the course of
ALL are called adult protocols and adult regimens. treatment.
Many of the same drugs are used for children and In contrast, adult regimens tend to be less intense.
older adults with ALL. But, the doses and schedules The types and doses of drugs used in adult regimens
are different. AYAs are patients aged 15 to 39. are meant to be tolerable for people across a wide
Importantly, studies show that AYAs have much better age range. AYAs treated with these regimens may be
outcomes when treated more like children. under-dosed.
Experts recommend that treatment for AYAs should Length of treatment: In pediatric protocols,
be based on pediatric protocols. This is referred to treatment is given for a longer period of time overall.
as a pediatric-inspired protocol. The main differences CNS preventive treatment is started earlier and given
between pediatric and adult treatments are described longer. Children often receive maintenance therapy
below. for about three years. Adult regimens tend to give
maintenance for about two years.
Differences between pediatric and adult treatment
regimens Side effects of chemotherapy
Drug dosage: Pediatric regimens are more intense A side effect is an unhealthy or unpleasant physical
and complex than those given to older adults. They or emotional condition caused by treatment. Each
use high (intensified) doses of certain chemotherapy treatment for ALL can cause side effects. The
drugs that can be hard for older adults to tolerate. reactions to chemotherapy differ between people.
Drugs used: Pediatric regimens tend to use Some people have many side effects. Others have
more pegaspargase, vincristine, and steroids such few. Some side effects can be very serious while
as dexamethasone and prednisone. Overall, the others can be unpleasant but not serious.
doses of these drugs are higher than what is given

36
Order of treatments
The treatment of ALL is a long-term process that lasts two to three years. ALL
treatment is given in three main steps, called phases. The length of each phase may
vary based on the intensity of the treatments and other factors.
Induction CNS prevention and

treatment
The first phase of ALL treatment is called induction.
This phase may also be called by other names such CNS (central nervous system) prevention
as remission induction or induction therapy. The goal and treatment is started during induction.
of induction therapy is to kill as many leukemia cells as It is given throughout all phases of ALL
possible. It is meant to cause (induce) a remission. A treatment. This part of treatment is also
remission is when no leukemia cells can be seen in blood referred to as CNS prophylaxis. CNS
or bone marrow viewed with a microscope and blood cell treatment is given to keep ALL from
counts are back to normal. The induction phase often lasts spreading to the area around the brain and
about four weeks (one month). You may need to stay in spinal cord. When leukemia cells are found
the hospital for some or most of this time. in this area, it is called CNS disease.

CONSOLIDATION Maintenance

The second phase of ALL treatment is called The third phase of ALL treatment is called
consolidation. This phase may also be called maintenance. The goal of maintenance
by other names such as intensification or therapy is to keep ALL from coming back.
postremission consolidation. Consolidation Most maintenance drugs are given orally, and
therapy is given once ALL is in remission. patients are usually treated in an outpatient
The goal of consolidation therapy is to kill any setting. The lower doses tend to have less
leukemia cells that may still be in your body. severe side effects. The maintenance phase
During this phase, treatments are intensified. lasts about two to three years. Consolidation
This means that drugs are given in higher doses and maintenance are often jointly called
than during induction. The consolidation phase postremission therapy. Postremission therapy
often lasts for a few months. refers to any treatments given after ALL is in
complete remission.

37
Most side effects appear soon after treatment starts Not all side effects of chemotherapy are listed here.
and will go away after treatment ends. But, other side Be sure to ask your treatment team for a complete
effects are long-term and may appear years later. list of common and rare side effects. If a side effect
bothers you, tell your treatment team. There may be
The side effects of chemotherapy depend on many ways to help you feel better. There are also ways to
factors. This includes the drug, the dose, and the prevent some side effects.
person. In general, side effects are caused by the
death of fast-growing cells, which are found in the
intestines, mouth, and blood. Thus, common side
effects of chemotherapy are nausea, vomiting,
diarrhea, mouth sores, not feeling hungry, hair loss,
and low blood cell counts. Feeling very tired (fatigue)
is also common.

38
Treatment response
A treatment response is an outcome or improvement caused by treatment. Doctors first

check for a treatment response at the end of induction therapy. To check how well treatment
worked, your doctor will test a sample of blood and bone marrow with a microscope. The
goal of ALL treatment is to result in a complete remission.
Even with a complete remission, there may still be a small number of leukemia cells left in the
body that cant be seen with a microscope. This is called MRD (minimal residual disease). Once
ALL is in complete remission, very sensitive tests are used to check for MRD.
After a complete remission, more treatment is needed to kill every last leukemia cell and keep
them from coming back. This is called postremission therapy. A relapse is when ALL comes back
after a complete remission. Sometimes the leukemia cells dont respond to induction therapy.
ALL that is not in complete remission after induction is called refractory ALL.
A complete remission is when:
No leukemia cells are seen in your bone marrow with a microscope,

No more than 5 out of 100 cells in your bone marrow are blast cells,
No blast cells are in your bloodstream,
All blood cell counts are back to normal, and
All signs and symptoms of ALL are gone.

39
4 Overview of cancer treatments Targeted therapy
Targeted therapy A number of factors may cause or lead to secondary

resistance. Most often, it is caused by mutations in
Targeted therapy is treatment with drugs that target the part of the BCR-ABL gene that makes the BCR-
a specific or unique feature of cancer cells. Because ABL protein. These mutations change the shape of
these drugs specifically target cancer cells, they may the BCR-ABL protein. This can affect how well certain
be less likely to harm normal cells throughout your TKIs work. New mutations can happen over time
body. The targeted therapy drugs that are used for during TKI therapy. This can cause the TKI to stop
ALL are listed in Chart 4.2 and are described next. working.
Tyrosine kinase inhibitors But, each TKI drug works in a slightly different way.
One TKI drug may be able to work against a mutation
TKI (tyrosine kinase inhibitor) therapy is a type of that another TKI cant. Therefore, switching to a
targeted therapy. TKIs are used for a subtype of ALL different TKI may result in a treatment response after
in which the leukemia cells have the Philadelphia a prior TKI stops working.
chromosome. This subtype is called Ph-positive ALL.
The Philadelphia chromosome contains the abnormal Side effects of TKIs
BCR-ABL fusion gene. Some side effects listed below are caused by only
one TKI. Others are caused by all or most TKIs but
TKIs target the abnormal BCR-ABL protein that helps differ in how likely they are to occur. Some common
leukemia cells grow. This protein is made by the side effects of TKIs are low blood cell counts,
BCR-ABL gene. It is a type of protein called a tyrosine abnormal bleeding, fatigue, nausea and vomiting,
kinase. TKIs block (inhibit) the BCR-ABL protein from diarrhea, and stomach or belly pain.
sending the signals that cause too many leukemia
cells to form. These drugs may cause swelling due to fluid buildup
around the eyes or in the hands and feet. Fluid may
TKIs are made in the form of a pill that is swallowed. also collect around the lungs. Other common side
TKIs are typically not used alone to treat ALL. Instead, effects include skin rashes, headaches, and muscle,
a TKI is added to a combination chemotherapy bone, and joint pain. A rare but serious side effect that
regimen. The use of TKIs has greatly improved may happen with TKIs is a change in the rhythm of
treatment outcomes for this type of ALL. your heartbeat.
TKI drug resistance Other rare but serious side effects may be caused by
A treatment response is an improvement in disease certain TKIs. For example, dasatinib may cause fluid
that is caused by treatment. Drug resistance is when buildup around the lungs. Nilotinib may cause the
ALL doesnt respond to a drug. There is more than amount of sugar (glucose) in the blood to be higher
one type of drug resistance. than normal. Serious side effects of ponatinib include
heart problems, blood clots, narrowing of blood
Primary resistance is when ALL doesnt respond vessels, heart attack, and stroke. Liver problems or
at all to a drug taken for the first time. This type of inflammation of the pancreas may also happen.
resistance is rare in ALL. Secondary resistance is
more common. It is when ALL responds to a drug at
first and then stops responding over time.

40
4 Overview of cancer treatments Targeted therapy
Chart 4.2 Targeted therapy drugs for ALL
Generic name Brand name (sold as) Type of drug
Imatinib Gleevec TKI
Dasatinib Sprycel TKI
Ponatinib Iclusig TKI
Nilotinib Tasigna TKI
Blinatumomab Blincyto Monoclonal antibody
Rituximab Rituxan Monoclonal antibody
Monoclonal antibodies Blinatumomab is a liquid that is slowly injected into

Monoclonal antibodies are another type of targeted a vein over 28 days. This is called a continuous
therapy used for ALL. A monoclonal antibody is a infusion. Blinatumomab should only be given in a
type of immune system protein that is made in a lab. cancer center that has experience with this drug. You
Monoclonal antibodies attach (bind) to proteins on may need to stay in the hospital for the first few days
cancer cells. Most monoclonal antibodies can bind to of treatment.
only one protein.
Side effects of this drug are fever, skin rash, nausea,
Blinatumomab diarrhea, constipation, swelling of the hands and feet,
Approved in December 2014, blinatumomab is one headache, and shaking (tremor). It can also cause
of the newest treatments for ALL. It is a monoclonal low white blood cell counts, which increases the risk
antibody that may be used for certain patients with of infection.
B-cell ALL after other treatments didnt work well.
Though uncommon, a severe reaction during
Blinatumomab is a special kind of antibody that can the infusion may happen. This can cause trouble
bind to two proteins at the same time. It binds to a breathing, headache, feeling dizzy or lightheaded, low
protein called CD19 that is found on immature B-cells blood pressure, fever, chills, and face swelling. Other
and some leukemia cells. It also binds to a protein less common but serious side effects are seizures,
called CD3 that is found on normal T-cells. T-cells trouble speaking or slurred speech, passing out,
are part of the bodys immune system. By binding to confusion, and loss of balance.
these two proteins, blinatumomab links the T-cells to
the leukemia cells. This helps the immune system find
and kill the leukemia cells.

41
4 Overview of cancer treatments Stem cell transplant
Rituximab Stem cell transplant

Rituximab is a monoclonal antibody that may be used
to treat certain patients with B-cell ALL. It binds to An SCT (stem cell transplant) is a treatment that
a protein called CD20. This protein is found on the destroys cells in the bone marrow then replaces
surface of normal and abnormal B-cells. And, it is them with new, healthy blood-forming cells. These
found on the leukemia cells of about half of adults blood-forming cells are called blood stem cells or
with B-cell ALL. hematopoietic stem cells. This treatment is also called
a hematopoietic cell transplant.
When rituximab binds to CD20, it sends a signal to
the cell to die. It also marks the cells for destruction The goal of an SCT is to cure cancer by replacing
by the immune system. Rituximab is not used alone unhealthy blood stem cells with healthy ones that will
to treat ALL. Instead, it is added to a chemotherapy attack cancer cells. This is done by suppressing the
combination regimen. It is given as a liquid that is bone marrow and cancer with chemotherapy then
slowly injected into a vein. transplanting healthy blood stem cells. The healthy
blood stem cells will grow, form new bone marrow
You may have an allergic reaction while receiving and blood cells, and attack remaining cancer cells.
rituximab. Other common side effects are chills,
infections, body aches, tiredness, and low blood cell For the treatment of ALL, blood stem cells from a
counts. Rituximab rarely increases the chance of donor are used for the transplant. This is called an
developing TLS, heart problems, and blockage and allogeneic SCT. Before the transplant, special testing
holes in your intestines. must be done to make sure the donor is a good
match for you. HLA typing is used to find a persons
tissue type, called an HLA type. (See page 17 for
more details on HLA typing.)
An allogeneic SCT creates a new immune system

for your body. Another benefit of this transplant is the
GVL (graft-versus-leukemia) effect. The GVL effect
is an attack on the leukemia cells by the transplanted
blood stem cells. The steps of treatment with an
allogeneic SCT are described next.
Conditioning treatment
Before the transplant, you will receive high-dose
chemotherapy and maybe high-dose radiation
therapy. This is called conditioning treatment since
it prepares (conditions) your body to receive the
donated blood stem cells.
The chemotherapy is given to destroy any remaining

leukemia cells in your bone marrow. But, it also
destroys normal blood cells in your bone marrow. This

42
4 Overview of cancer treatments Stem cell transplant
greatly weakens your immune system so that your An allogeneic SCT is not used as the first or
body doesnt kill the transplanted blood stem cells. main treatment for ALL. It may be used as part
of consolidation therapy for certain patients with
For some patients, lower doses of chemotherapy or Ph-positive ALL or in patients with other poor risk
radiation may be used before the transplant. This features. Doctors may also consider an allogeneic
is called non-myeloablative or reduced-intensity SCT if prior treatments fail to kill all of the leukemia
conditioning. This type of conditioning may be a good cells or keep them away.
option for certain patients who are older or in poorer
health. It can often work just as well as high-dose Side effects of allogeneic SCT
conditioning. A side effect is an unhealthy or unpleasant physical
or emotional condition caused by treatment. Common
Transplanting the stem cells side effects of chemotherapy, which is given before
After the chemotherapy, the blood stem cells will be the transplant, are described on page 36. You will
put into your body with a transfusion. A transfusion is likely feel tired and weak shortly after the transplant
a slow injection of blood products into a large vein. while waiting for the new blood stem cells to grow in
This process can take several hours to complete. the bone marrow.
The transplanted stem cells then travel to your bone Allogeneic transplants have a high risk of GVHD
marrow and grow. They will make new, healthy blood (graft-versus-host disease). GVHD is when
cells. This is called engraftment. It usually takes about the donated cells see the cells in your body as
2 to 4 weeks. foreign and attack them. The parts of the body
most commonly damaged by GVHD are the skin,
Until then you will have little or no immune defense. intestines, and liver.
This puts you at high risk for infection and bleeding.
You will likely need to stay in a hospital in a very GVHD is a serious side effect that can cause the
clean room for some time. It may take a few weeks transplant to fail by stopping the donated blood stem
or months for blood cells to fully recover so that your cells from growing in your bone marrow. GVHD can
immune system is back to normal. happen within a few weeks after the transplant or
much later. Your doctor may give you medicine that
Considering allogeneic SCT suppresses your immune system to try to prevent this
An allogeneic SCT is a complex treatment and can side effect.
cause very serious side effects. Thus, it may not
be a good treatment choice for every patient with
ALL. Many treatment centers will only consider this
treatment option for patients younger than 65 years
of age.
Your doctor will look at many factors to help decide

if an allogeneic SCT is a good choice for you. These
factors include your age and general health, certain
prognostic factors, how well other treatments worked,
and if a well-matched donor has been found.

43
4 Overview of cancer treatments Radiation therapy
Radiation therapy
Radiation therapy uses high-energy rays to treat
cancer. The rays damage the genes in cells. This
either kills the cancer cells or stops new cancer cells
from being made. Radiation therapy may be given
in different ways. For ALL, radiation therapy is given
from a machine outside the body. This method is
called EBRT (external beam radiation therapy).
Radiation therapy is not usually part of the main

treatment for ALL. But, it may be used to treat leukemia
cells that have spread to fluid around the brain and
spinal cord. This is called CNS disease. To treat CNS
disease, radiation therapy is aimed at the brain and/or
spine. Doctors may refer to this as cranial irradiation or
cranial-spinal irradiation. Radiation therapy may also
be used to treat leukemia cells that have spread to the
testicles. Lastly, radiation therapy can be used as part
of the treatment given prior to an SCT.
During treatment, you will lie down on a treatment

table and stay very still. You will be alone while a
technician operates the EBRT machine from a nearby
room. The technician will be able to see, hear, and
speak with you at all times. As treatment is given, you
may hear noises. A session can take between 15 and
30 minutes. Radiation therapy is often given 5 days a
week for 23 weeks.
Side effects of radiation therapy

Side effects of radiation therapy depend on the dose
and the area of your body being treated. Most of the
side effects go away soon after treatment ends. Some
of the most common side effects of radiation therapy
include:
Skin changes,
Hair loss,
Fatigue,
Upset stomach, and
Diarrhea.

44
4 Overview of cancer treatments Supportive care
Supportive care Infection risks

ALL and its treatment can cause very low white blood
Supportive care is treatment given to relieve the cell counts. White blood cells are part of the immune
health problems caused by cancer and side effects system and help fight off infection and disease.
of cancer treatment. Managing symptoms and side Having a very low white blood cell count puts you at
effects with supportive care is important for your risk for infections.
quality of life and treatment outcome. Supportive
care options for common health problems that affect Medicines may be given to prevent or treat infections.
patients with ALL are described next. Antibiotics can prevent or treat infections caused
by bacteria. An antifungal is medicine for infection
Nausea and vomiting caused by fungus. An antiviral is medicine for
Many chemotherapy drugs can cause nausea and infection caused by a virus. Your doctor may also
vomiting. Medicine can be given to lessen or prevent suggest that you get vaccines for pneumonia and the
this side effect. Drugs that prevent nausea and flu.
vomiting are called antiemetics. Antiemetics should
be given before starting chemotherapy treatment. Tumor lysis syndrome
TLS (tumor lysis syndrome) is a rare condition that
Low blood cell counts occurs when many cancer cells die very quickly due
ALL and its treatment can cause low blood cell to cancer or its treatment. Chemotherapy may destroy
counts. Very low blood cell counts can cause a large numbers of leukemia cells quickly. As the cells
number of health problems. But, there are many ways die, they break down and release their contents
to manage this side effect. into the blood. This changes the normal balance of
chemicals in the blood. It can cause very high levels
A low number of red blood cells can cause fatigue of certain chemicals.
and shortness of breath. If your red blood cell count is
low, you may be given a transfusion of red blood cells. Uric acid is one of the chemicals released by dying
A low number of platelets can cause you to bleed or cancer cells. Very high levels of uric acid and other
bruise easily. A transfusion of platelets may be given if chemicals can be very bad for the body. It can cause
your platelet count is very low. severe damage to organs such as the kidneys and
heart. Drugs such as allopurinol and rasburicase may
Having a low number of white blood cells is also very be given to prevent or lessen the effects of TLS.
common during treatment for ALL. Transfusions are
not used to treat low white blood cell counts. Instead,
you may be given a type of drug called a growth
factor.
Growth factors help the bone marrow to make new

healthy white blood cells. This helps to increase the
white blood cell count quickly. Growth factors are
recommended during parts of ALL treatment that
lower (suppress) the bone marrows ability to make
new blood cells.

45
4 Overview of cancer treatments Review
Review
Treatment for ALL is given in steps, called A clinical trial studies a test or treatment
phases: induction, consolidation, and to see how safe it is and how well it
maintenance. works. Clinical trials are how we learn
which treatments are best. NCCN experts
CNS preventive treatment is given during all
recommend that you should strongly consider
phases of treatment.
taking part in a clinical trial if one is available
The main treatment of ALL involves long-term to you.
use of chemotherapy.
Treatment for AYA patients should be based
Chemotherapy is treatment with drugs that on regimens which have been highly effective
kill fast-growing cells, including leukemia cells for children with ALL.
and normal cells.
Supportive care is treatment given to relieve
Targeted therapy drugs specifically target the symptoms of cancer or side effects of
cancer cells. cancer treatment. Supportive care is an
important part of overall cancer treatment.
A stem cell transplant replaces damaged or
diseased bone marrow with healthy donor
blood stem cells.

46
5
Treatment guide

47
5 Treatment guide
50 5.1 AYAs with Ph-negative ALL
Treatment options for AYAs when
the leukemia cells do not have the
Philadelphia chromosome.
54 5.2 Older adults with Ph-

negative ALL
Treatment options for older adults
when the leukemia cells do not have
the Philadelphia chromosome.
58 5.3 AYAs with Ph-positive ALL

Treatment options for AYAs when
the leukemia cells have the
abnormal Philadelphia chromosome.
62 5.4 Older adults with Ph-

positive ALL
Treatment options for older adults
when the leukemia cells have the
abnormal Philadelphia chromosome.
66 5.5 Follow-up after treatment

for ALL
Lists the tests and schedule
of follow-up care needed after
completing treatment.
68 5.6 Relapsed and refractory

ALL
Treatment options for ALL that didnt
respond to treatment or came back
after a complete remission.

48
5 Treatment guide Acute lymphoblastic leukemia
NCCN experts recommend that all patients

Part 5 is a guide through the receive treatment in a specialized cancer
center with expertise and experience in ALL.
treatment options for patients with The treatment of ALL is very complex. Its important
ALL. However, these treatments to be cared for by a multidisciplinary team of experts
with experience in treating patients your age.
may also be used for patients
with lymphoblastic lymphoma. Access to clinical trials is also a chief priority.
This information is taken from the Specialized cancer centers, such as large academic
centers, have the experts, experience, and research
treatment guidelines written by NCCN to provide the best care for patients with ALL.
experts of ALL. These treatment
guidelines list options for people with
Treatment options
ALL in general. Your doctors may There are multiple treatment options for ALL.
suggest other treatment for you based Treatment options that are best for you depend on a
number of factors. This includes the features of the
on your health and personal wishes. cancer, such as the cytogenetic subtype, as well as
Fully discuss your treatment options your age and health status.
with your doctor.
The treatment options in Part 5 are grouped by
patient age and presence of the Philadelphia
chromosome. The type and intensity of treatment
Much effort has been made to make this guide easy differs based on your age and health. To plan
to read. Charts list the treatment options and map the treatment, doctors put patients into two main age
steps through the treatment process. The text along groups.
with each chart explains the information shown in the
chart. The AYA (adolescent and young adult) group includes
patients who are 15 to 39 years of age. The older
adult group includes patients who are 40 years of age
or older. The other main factors that affect treatment
planning and options are described in Part 3 on page
26.

49
3
5 Treatment
DCIS guide Genetic
AYAscounseling
with Ph-negative
| Treatment
ALL
5.1 AYAs with Ph-negative ALL
Chart 5.1.1 Remission induction for AYAs with Ph-negative ALL
Induction therapy options Response Next options
Clinical trial,
Complete remission Monitor for MRD
Pediatric-inspired chemotherapy
regimen (preferred), or
Other multiagent Less than complete remission Treatment for refractory ALL
chemotherapy regimen
Chart 5.1.1 shows the induction therapy options A regimen based on treatment designed for children
for AYAs with Ph-negative ALL. Induction therapy is with ALL is preferred. This is called a pediatric-
the first phase of treatment for ALL. It is also called inspired regimen or a pediatric-inspired protocol. But,
remission induction. The goal is to kill all of the other multiagent chemotherapy regimens that have
leukemia cells in your bone marrow and put ALL into been studied in AYAs may also be used.
complete remission.
Pediatric-inspired induction regimens tend to use a
Induction therapy consists of high doses of combination of vincristine, pegaspargase, a steroid
chemotherapy drugs. It is very intensive and lasts (prednisone or dexamethasone), and an anthracycline
about four weeks (one month). You may need to stay (doxorubicin or daunorubicin). Some regimens may
in the hospital for some or all of the time during this also include cyclophosphamide and etoposide. (See
treatment. page 34 to read more about chemotherapy drugs.)
Pediatric-inspired regimens often start CNS

Induction therapy options preventive treatment very early at the start of the
induction phase. For CNS treatment, drugs are often
In general, there are three main options to choose injected into the spinal fluid during a lumbar puncture.
from for induction therapy. Treatment within a clinical When drugs are given this way, it is called IT therapy
trial is preferred if one is open and is the right fit for or IT chemotherapy.
you. The other options are to receive multiagent
chemotherapy outside of a clinical trial. CNS treatment may include IT methotrexate alone
or with other drugs such as IT cytarabine and an IT

50
5 Treatment guide AYAs with Ph-negative ALL
steroid (dexamethasone or prednisone). When all

three drugs are given, it is called triple IT therapy.
Methotrexate, cytarabine, and 6-MP may also be
Next steps:
given as IV injections for CNS treatment. Rarely, CNS
disease may be found when ALL is first diagnosed. If induction therapy resulted in a
In this case, your doctor may consider giving cranial
complete remission, see Chart 5.1.2
irradiation as well.
on page 52 for the next options. If
induction therapy resulted in less than
Response and next options
a complete remission, see Chart 5.6.1
At the end of induction, your doctor will assess how on page 68 for the next options.
well treatment worked. A treatment response is an
outcome or improvement caused by treatment. To
check the response, your doctor will test a sample
of blood and bone marrow with a microscope. A
complete remission is when no leukemia cells are
seen in the blood or bone marrow and all signs and
symptoms of ALL are gone. (See page 39 for more
details about treatment responses.)
If tests show a complete remission, then your

doctor may test for MRD. MRD is when a very small
amount of leukemia cells remains in your body
after a course of treatment. With MRD, the amount
of leukemia cells left is too small to be seen with a
microscope.
PCR and flow cytometry are very sensitive tests that

doctors use to check for MRD. These tests can detect
a single leukemia cell among more than 10,000 normal
cells. They can be done on a sample of blood or bone
marrow. Bone marrow is usually preferred. Testing for
MRD can help your doctor decide if more intensive
treatments are needed during consolidation therapy.
If tests show less than a complete remission, this

means treatment wasnt able to kill enough leukemia
cells in your body. ALL that is not in complete
remission after induction is called refractory ALL. In
this case, treatment with other drugs or regimens will
be tried. See Next steps at the end of this section.

51
Chart 5.1.2 Postremission consolidation and maintenance
Consolidation therapy options Next options
Maintenance therapy for 2 to 3 years with:

Continue multiagent Weekly methotrexate,
chemotherapy regimen, or Daily 6-MP, and
Monthly vincristine/prednisone pulses
Consider allogeneic SCT Start follow-up testing
Chart 5.1.2 shows the treatment options for AYAs multiagent chemotherapy as outlined in the pediatric-
with Ph-negative ALL in complete remission after inspired regimen. This may be an especially good
induction therapy. Consolidation therapy is the second choice if no leukemia cells were found by MRD
phase of treatment for ALL. The goal of this phase is testing.
to kill any leukemia cells that may still be in your body.
It is followed by maintenance therapy. These phases Consolidation therapy may include combinations of
are jointly referred to as postremission therapy since drugs similar to those used for induction. In pediatric-
they are given after ALL is in remission. inspired regimens, it tends to include high-dose
methotrexate, cytarabine, 6-MP, and pegaspargase.
Your doctor will look at many factors to help plan Chemotherapy drugs are given in higher (intensified)
consolidation therapy. This includes the ALL cell doses during consolidation. CNS preventive treatment
subtype, chromosome changes, results of MRD is also usually given throughout this phase of
testing, and other prognostic factors. Your general treatment.
health, current symptoms, and side effects will
also be considered. This can help to decide if you Consolidation therapy may last several months.
need and can tolerate more intensive treatment for How long it lasts and the total number of cycles
consolidation. varies based on the regimen used. The full treatment
regimen should be followed all the way through
consolidation and to the end of maintenance.
Consolidation therapy options
The other option is to consider an allogeneic SCT.
There are two main options to choose from for This is a very intensive treatment performed in
consolidation therapy. The first option is to stay on specialized centers, and may not be a good choice

52
for everyone. (See page 42 to read more about

allogeneic SCT.) Your doctor may consider this option
if tests found MRD after induction. This may also be
Next steps:
a good choice if the leukemia cells have certain poor
risk features. A poor risk feature is something that After the allogeneic SCT or after
increases the chance that ALL might come back after
completing consolidation and
treatment. Examples of poor risk features include
having less than the normal number of chromosomes maintenance therapy, see Chart 5.5
or having five or more abnormal chromosome on page 66 for follow-up testing.
changes.
Next options and maintenance therapy
After consolidation with an allogeneic SCT, you

will begin follow-up testing. See Next steps at the end
of this section.
After consolidation with multiagent

chemotherapy, you will receive maintenance
therapy. Maintenance therapy is the third phase
of ALL treatment. Maintenance therapy is given to
keep (maintain) the good results of prior treatments.
The goal is to prevent a relapse after induction and
consolidation therapy. A relapse is when leukemia
cells come back after a complete remission.
Most maintenance regimens are based on a

backbone of daily 6-MP and weekly methotrexate.
Often, vincristine and a steroid (prednisone or
dexamethasone) are also given. Maintenance therapy
drugs are often given in lower doses and cause fewer
side effects. CNS preventive treatment can also be
given throughout the maintenance phase.
In general, maintenance therapy is given for about

two to three years. But, the total length varies based
on the treatment regimen used. Pediatric-inspired
regimens tend to give maintenance therapy for a
longer time than adult regimens.

53
3
5 Treatment
DCIS guide Older
Genetic counseling
adults with
| Treatment
Ph-negative ALL
5.2 Older adults with Ph-negative ALL
Chart 5.2.1 Remission induction for older adults with Ph-negative ALL
Health status Induction therapy options Response
Clinical trial, or Complete remission, monitor for MRD

Patients <65 years of age
or patients with no other
Multiagent chemotherapy
serious health problems
regimen for adults Less than complete remission
Clinical trial,
Complete remission, monitor for MRD
Patients 65 years of age
or patients with other
regimen for adults, or
serious health problems
Less than complete remission
Corticosteroids
Chart 5.2.1 shows the induction therapy options for CNS treatment may include IT methotrexate alone
older adults with Ph-negative ALL. Induction therapy or with other drugs such as IT cytarabine and an IT
is the first phase of treatment for ALL. It is also called steroid (dexamethasone or prednisone). When all
remission induction. The goal is to kill all of the three drugs are given, it is called triple IT therapy.
leukemia cells in your bone marrow and put ALL into Methotrexate, cytarabine, and 6-MP may also be
complete remission. given as IV injections for CNS treatment. Rarely, CNS
disease may be found when ALL is first diagnosed.
Induction therapy consists of high doses of In this case, your doctor may consider giving cranial
chemotherapy drugs. It is very intensive and lasts irradiation as well.
about four weeks (one month). You may need to stay
in the hospital for some or all of the time during this
treatment. Induction therapy options
CNS preventive treatment is given to all patients Often, age 65 is the cut-off for intensive treatment.
during the induction phase. For CNS treatment, drugs But, age alone is not a good gauge of a persons
are often injected into the spinal fluid during a lumbar overall health or fitness for intensive treatment. When
puncture. When drugs are given this way, it is called choosing an induction regimen, your doctors will
IT therapy or IT chemotherapy. look at your age, general health, organ function, and

54
5 Treatment guide Older adults with Ph-negative ALL
other current health conditions. This will help your If tests show a complete remission, then your
doctor to know if you are able to receive very strong doctor may test for MRD. MRD is when a very small
treatments. amount of leukemia cells remains in your body
If you are younger than age 65, or you dont have of leukemia cells left is too small to be seen with a
other serious health problems, there are two main microscope.
options to choose from. Treatment within a clinical
trial is preferred if one is open and is the right fit PCR and flow cytometry are very sensitive tests that
for you. The other option is to receive multiagent doctors use to check for MRD. These tests can detect
chemotherapy based on a regimen designed for a single leukemia cell among more than 10,000
adults. Induction regimens for adults tend to use a normal cells. They can be done on a sample of blood
combination of vincristine, a steroid (prednisone or or bone marrow. But, bone marrow is preferred.
dexamethasone), cyclophosphamide, and doxorubicin Testing for MRD can help your doctor decide if more
or daunorubicin. intensive treatments are needed for consolidation.
If you are age 65 or older, or you have other If tests show less than a complete remission, this
serious health problems, there are three main means treatment wasnt able to kill enough leukemia
options to choose from. Treatment within a clinical cells in your body. ALL that is not in complete
trial is preferred if one is open and is the right fit remission after induction is called refractory ALL. In
for you. The second option is to have multiagent this case, treatment with other drugs or regimens will
chemotherapy based on a regimen for adults as be tried. See Next steps at the end of this section.
described above. The third option is treatment
with corticosteroids such as prednisone or
dexamethasone. These drugs may be easier to take
than chemotherapy. Some patients may not be able
to tolerate the side effects of intensive (high-dose)
regimens. If needed, some chemotherapy drugs may
Next steps:
be given in lower doses to lessen the side effects.
If induction therapy resulted in a
Response
At the end of induction, your doctor will assess how induction therapy resulted in less than
check the response, your doctor will test a sample on page 68 for the next options.

55
Health status Consolidation therapy options Maintenance therapy options
Maintenance for 2 to 3 years with:

Patients <65 years Continue multiagent Weekley methotrexate,
of age or patients chemotherapy regimen, or Daily 6-MP, and
with no other serious Monthly vincristine/prednisone pulses
health problems
Consider allogeneic SCT Start follow-up testing
Patients 65 years Maintenance for 2 to 3 years with:

of age or patients Continue multiagent Weekley methotrexate,
with other serious chemotherapy regimen Daily 6-MP, and
health problems Monthly vincristine/prednisone pulses
Chart 5.2.2 shows the treatment options for older need and can tolerate more intensive treatment for
adults with Ph-negative ALL in a complete remission consolidation.
after induction therapy. Consolidation therapy is the
second phase of treatment for ALL. The goal of this If you are younger than age 65, or you dont have
phase is to kill any leukemia cells that may still be other serious health problems, there are two main
in your body. It is followed by maintenance therapy. options to choose from. One option is to stay on the
These phases are jointly referred to as postremission multiagent chemotherapy regimen for consolidation
therapy since they are given after ALL is in remission. and maintenance. This may be an especially good
choice if no leukemia cells were found by MRD
testing.
Consolidation therapy options
Consolidation therapy may include combinations of
Your doctor will look at many factors to help plan drugs similar to those used for induction. In regimens
consolidation therapy. This includes the ALL cell designed for adults, it tends to include drugs such as
subtype, chromosome changes, results of MRD methotrexate, cytarabine, and 6-MP. Chemotherapy
testing, and other factors described in Part 3. Your drugs are given in higher (intensified) doses during
general health, current symptoms, and side effects consolidation. CNS preventive treatment is also
will also be noted. This can help to decide if you usually given throughout this phase of treatment.

56
Consolidation therapy may last several months. After consolidation with multiagent
How long it lasts and the total number of cycles chemotherapy, you will receive maintenance
varies based on the regimen used. The full treatment therapy. Maintenance therapy is the third phase of
regimen should be followed all the way through ALL treatment. Maintenance therapy is given to keep
consolidation and to the end of maintenance. up (maintain) the good results of prior treatments.
The goal is to prevent a relapse after induction and
The other option is to consider an allogeneic SCT. consolidation therapy. A relapse is when leukemia
This is a very intensive treatment performed in cells come back after a complete remission.
specialized centers, and may not be a good choice
for everyone. It can cause very severe side effects Most maintenance regimens are based on a
that may be too much for some patients to take. Your backbone of daily 6-MP and weekly methotrexate.
doctor will look at a number of factors to assess if Often, vincristine and a steroid (prednisone or
an allogeneic SCT is a good choice for you. This dexamethasone) are also given. Maintenance therapy
includes your age, general health, and if you can drugs are often given in lower doses and cause fewer
tolerate intensive treatments. (See page 42 to read side effects. CNS preventive treatment can also be
more about allogeneic SCT.) given throughout the maintenance phase.
Your doctor may consider this option if tests found In general, maintenance therapy is given for about
MRD after induction. This may also be a good choice two to three years. But, the total length varies based
if the leukemia cells have certain poor risk features. on the treatment regimen used. Adult regimens tend
A poor risk feature is something that increases the to give maintenance therapy for a shorter amount of
chance that ALL might come back after treatment. time than pediatric-inspired regimens.
Examples of poor risk features include having less
than the normal number of chromosomes or having
five or more abnormal chromosome changes.
If you are age 65 or older, or you have other

serious health problems, there is one main
Next steps:
option for consolidation. The option is to stay on
a chemotherapy regimen for consolidation as After the allogeneic SCT or after
described above for adults younger than age 65.
completing consolidation and
Allogeneic SCT is a very intense treatment and can
cause very severe side effects. Thus, it is often not maintenance therapy, see Chart 5.5
recommended if you are older than 65 or you have on page 66 for follow-up testing.
other serious health problems.
Maintenance therapy options
After consolidation with an allogeneic SCT, you

will begin follow-up testing. See Next steps at the end
of this section.

57
3
5 Treatment
DCIS guide Genetic
AYAscounseling
with Ph-positive
| Treatment
ALL
5.3 AYAs with Ph-positive ALL
Chart 5.3.1 Remission induction for AYAs with Ph-positive ALL
Induction therapy options Response Next options
Complete remission Monitor for MRD

Clinical trial, or
regimen + TKI
Less than complete remission Treatment for refractory ALL
Chart 5.3.1 shows the induction therapy options TKIs are a type of targeted therapy. TKIs block the
for AYAs with Ph-positive ALL. Induction therapy is cancer-causing action of the BCR-ABL fusion gene.
the first phase of treatment for ALL. It is also called This gene is found on the Philadelphia chromosome.
remission induction. The goal is to kill all of the The use of TKIs has greatly improved treatment
leukemia cells in your bone marrow and put ALL into outcomes for Ph-positive ALL. Importantly, adding
complete remission. a TKI to the multiagent chemotherapy regimen
increases the chance of a complete remission. (See
Induction therapy consists of high doses of page 40 to read more about TKIs.)
chemotherapy drugs. It is very intensive and lasts
about four weeks (one month). You may need to stay Induction regimens for AYAs generally include a
in the hospital for some or all of the time during this combination of vincristine, pegaspargase, a steroid
treatment. (prednisone or dexamethasone), and an anthracycline
(doxorubicin or daunorubicin). Some regimens may
also include cyclophosphamide and etoposide.
Induction therapy options
CNS preventive treatment is given to all patients
In general, there are two main options to choose from during the induction phase. For CNS treatment, drugs
for induction therapy. Treatment within a clinical trial is are often injected into the spinal fluid during a lumbar
preferred if one is open and is the right fit for you. The puncture. When drugs are given this way, it is called
other option is to have a multiagent chemotherapy IT therapy or IT chemotherapy.
regimen combined with a TKI. Imatinib and dasatinib
are the main TKIs used for induction. CNS treatment may include IT methotrexate alone

58
5 Treatment guide AYAs with Ph-positive ALL
steroid (dexamethasone or prednisone). When all

three drugs are given, it is called triple IT therapy.
Methotrexate, cytarabine, and 6-MP may also be
Next steps:
given as IV injections for CNS treatment. Rarely, CNS
disease may be found when ALL is first diagnosed. If induction therapy resulted in a
In this case, your doctor may consider giving cranial
induction therapy resulted in less than
Response and next options
At the end of induction, your doctor will assess how on page 70 for the next options.
check the response, your doctor will test a sample
If tests show a complete remission, then your

doctor will test for MRD. MRD is when a very small
amount of leukemia cells remains in your body
of leukemia cells left is too small to be seen with a
microscope.
PCR and flow cytometry are very sensitive tests that

doctors use to check for MRD. These tests can detect
a single leukemia cell among more than 10,000
normal cells. They can be done on a sample of blood
or bone marrow. But, bone marrow is preferred.
Testing for MRD can help your doctor decide if more
intensive treatments are needed for consolidation.
If tests show less than a complete remission, this

means treatment wasnt able to kill enough leukemia
cells in your body. ALL that is not in complete
remission after induction is called refractory ALL. In
this case, treatment with other drugs or regimens will
be tried. See Next steps at the end of this section.

59
Consolidation therapy options Maintenance therapy options
Allogeneic SCT if a donor is available, or Consider maintenance therapy with a TKI
Maintenance therapy for 2 to 3 years with:

TKI (imatinib or dasatinib),
If an allogeneic SCT donor is not available,
Monthly vincristine/prednisone pulses,
continue multiagent chemotherapy regimen + TKI
Weekly methotrexate, and
Daily 6-MP
Chart 5.3.2 shows the treatment options for AYAs Consolidation therapy options
with Ph-positive ALL in complete remission after
induction therapy. Consolidation therapy is the second There are two main options for consolidation
phase of treatment for ALL. The goal of this phase is therapy. The first option is to have an allogeneic
to kill any leukemia cells that may still be in your body. SCT. This option is recommended if a well-matched
It is followed by maintenance therapy. These phases donor has been found. Consolidation with an
are jointly referred to as postremission therapy since allogeneic SCT may help keep ALL from coming
they are given after ALL is in remission. back after a complete remission. But, it is a very
intensive treatment and may not be a good choice
Your doctor will look at many factors to help plan for everyone. (See page 42 to read more about
consolidation therapy. This includes the ALL cell allogeneic SCT.)
subtype, chromosome changes, results of MRD
testing, and other prognostic factors. Your general Your doctor will look at a number of factors to decide
health, current symptoms, and side effects will also if an allogeneic SCT is a good choice for you. This
be noted. This can help to decide if you need and can includes your age, prognostic factors, and how well
tolerate more intensive treatment for consolidation. prior treatments worked. For some AYA patients, an
allogeneic SCT may offer the best chance of a long-
lasting remission. For other patients, an allogeneic
SCT might not be better than chemotherapy and a
TKI.

60
The second option is to stay on multiagent (prednisone or dexamethasone) are also given. A TKI
chemotherapy combined with a TKI. This option is such as imatinib or dasatinib should be added to the
suggested if a well-matched donor for the SCT has maintenance regimen your doctor plans for you.
not been found. This may also be a good option if
your doctor thinks an allogeneic SCT is too intense After consolidation with an allogeneic SCT,
for you. maintenance therapy with a TKI is recommended.
The TKI may be given alone. Or, it may be given
Consolidation therapy may include combinations of along with other drugs if the side effects arent too
drugs similar to those used for induction. A TKI should severe.
be added to the consolidation therapy regimen for all
patients with Ph-positive ALL. Imatinib and dasatinib Methotrexate and 6-MP can affect the liver and lower
are the main TKIs used for this phase. Staying on (suppress) the bone marrows ability to make new
treatment with a TKI can help keep ALL from coming blood cells. These side effects can be severe and
back after a complete remission. hard to tolerate. If needed, lower doses of these
drugs may be given to lessen the side effects.
Chemotherapy drugs are given in higher (intensified)
doses during consolidation. CNS preventive treatment Maintenance therapy drugs are often given in lower
is also usually given throughout this phase of doses and cause fewer side effects. CNS preventive
treatment. Consolidation therapy may last several treatment can also be given throughout this treatment
months. How long it lasts and the total number of phase. Maintenance therapy is given for about two
cycles varies based on the regimen used. The full to three years. But, the total length varies based on
treatment regimen should be followed all the way the regimen used. Pediatric-inspired regimens tend to
through consolidation and to the end of maintenance. give maintenance therapy for a longer time than adult
regimens.
Maintenance therapy options
The third phase of ALL treatment is called

maintenance. This phase is started after you finish
consolidation therapy. Maintenance therapy is
Next steps:
given to keep up (maintain) the good results of prior
treatments. The goal is to prevent a relapse after After completing consolidation and
induction and consolidation therapy. A relapse is
maintenance therapy, see Chart 5.5
when leukemia cells come back after a complete
remission. on page 66 for follow-up testing.
Staying on treatment with a TKI is key part of

maintenance therapy. Most maintenance regimens
include weekly methotrexate and daily 6-MP.
Often, monthly pulses of vincristine and a steroid

61
3
5 DCIS
Treatment guide Older
Genetic counseling
adults with
| Treatment
Ph-positive ALL
5.4 Older adults with Ph-positive ALL
Chart 5.4.1 Remission induction for older adults with Ph-positive ALL
Health status Induction therapy options Response
Patients <65 years Clinical trial, or Complete remission, monitor for MRD
of age or patients
with no other serious
health problems Less than complete remission
regimen + TKI
Clinical trial,
Patients 65 years Complete remission, monitor for MRD
of age or patients
TKI + corticosteroids, or
with other serious
health problems Less than complete remission
TKI + chemotherapy
Chart 5.4.1 shows the induction therapy options for steroid (dexamethasone or prednisone). When all
older adults with Ph-positive ALL. Induction therapy three drugs are given, it is called triple IT therapy.
is the first phase of treatment for ALL. It is also called Methotrexate, cytarabine, and 6-MP may also be
remission induction. The goal is to kill all of the given as IV injections for CNS treatment. Rarely, CNS
leukemia cells in your bone marrow and put ALL into disease may be found when ALL is first diagnosed.
complete remission. In this case, your doctor may consider giving cranial
Induction therapy consists of high doses of
chemotherapy drugs. It is very intensive and lasts
about four weeks. You may need to stay in the Induction therapy options
hospital some or all of the time during this treatment.
Often, age 65 is the cut-off for intensive treatment.
CNS preventive treatment is given to all patients But, age alone is not a good gauge of a persons
during the induction phase. For CNS treatment, drugs overall health or fitness for intensive treatment. When
are often injected into the spinal fluid during a lumbar choosing an induction regimen, your doctors will
puncture. When drugs are given this way, it is called look at your age, general health, organ function, and
IT therapy or IT chemotherapy. other current health conditions. This will help your
doctor to know if you are able to receive very strong
CNS treatment may include IT methotrexate alone treatments.

62
5 Treatment guide Older adults with Ph-positive ALL
If you are younger than age 65, or you dont seen in the blood or bone marrow and all signs and
have other serious health problems, there are symptoms of ALL are gone. (See page 39 for more
two main options to choose from. Treatment within a details about treatment responses.)
clinical trial is preferred if one is open and is the right
fit for you. The other option is to have a multiagent If tests show a complete remission, then your
chemotherapy regimen combined with a TKI. Imatinib doctor will test for MRD. MRD is when a very small
and dasatinib are the main TKIs used for induction. amount of leukemia cells remains in your body
TKIs are a type of targeted therapy. TKIs block the of leukemia cells left is too small to be seen with a
cancer-causing action of the BCR-ABL fusion gene. microscope.
This gene is found on the Philadelphia chromosome.
The use of TKIs has greatly improved treatment PCR and flow cytometry are very sensitive tests that
outcomes for Ph-positive ALL. Importantly, adding doctors use to check for MRD. These tests can detect
a TKI to the multiagent chemotherapy regimen a single leukemia cell among more than 10,000 normal
increases the chance of a complete remission. (See cells. They can be done on a sample of blood or bone
page 40 to read more about TKIs.) marrow. But, bone marrow is preferred. Testing for
MRD can help your doctor decide if more intensive
If you are age 65 or older, or you have other treatments are needed for consolidation therapy.
serious health problems, there are three main
options to choose from. Treatment within a clinical trial If tests show less than a complete remission, this
is preferred if one is open and is the right fit for you. means treatment wasnt able to kill enough leukemia
The second option is to have treatment with a TKI cells in your body. ALL that is not in complete
(imatinib or dasatinib) and a steroid. Prednisone and remission after induction is called refractory ALL. In
dexamethasone are the main steroids that may be this case, treatment with other drugs or regimens will
used. The third option is to receive a TKI along with a be tried. See Next steps at the end of this section.
multiagent chemotherapy regimen.
Steroids may be easier to take than chemotherapy.

Chemotherapy regimens can cause severe side
effects that may be very hard for some patients to
tolerate. If needed, chemotherapy drugs may be
Next steps:
given in lower doses to lessen the side effects.
If induction therapy resulted in a
Response
At the end of induction, your doctor will assess how induction therapy resulted in less than
check the response, your doctor will test a sample on page 70 for the next options.

63
Health status Consolidation therapy options Maintenance therapy options
Allogeneic SCT if a
Consider maintenance with a TKI
donor is available, or
Patients <65 years
of age or patients
Maintenance therapy with:
with no other serious
If allogeneic SCT donor is not TKI (imatinib or dasatinib),
health problems
available, continue multiagent Monthly vincristine/prednisone pulses,
chemotherapy regimen + TKI Weekly methotrexate, and
Daily 6-MP
Maintenance therapy with:

Patients 65 years Continue TKI corticosteroids, or
TKI (imatinib or dasatinib),
of age or patients
Monthly vincristine/prednisone pulses,
with other serious
Weekly methotrexate, and
health problems Continue TKI chemotherapy
Daily 6-MP
Chart 5.4.2 shows the treatment options for older If you are younger than age 65, or you dont have
adults with Ph-positive ALL after induction therapy other serious health problems, there are two main
resulted in a complete remission. Consolidation options to choose from. The first option is to have an
also called intensificationis the second phase of allogeneic SCT. This option is recommended if a well-
treatment for ALL. This may also be referred to as matched donor has been found. Consolidation with
postremission therapy since it is given after ALL is in an allogeneic SCT may help keep ALL from coming
complete remission. The goal of consolidation is to kill back after a complete remission. But, it is a very
any leukemia cells that may still be in your body. intensive treatment that may not be a good choice
for everyone. (See page 42 to read more about an
allogeneic SCT.)
Consolidation therapy
Your doctor will look at a number of factors to decide
Your doctor will look at many factors to help plan if an allogeneic SCT is a good choice for you. This
consolidation therapy. This includes the ALL cell includes your age, general health, and ability to
subtype, chromosome changes, results of MRD tolerate intensive treatments. For some patients, an
testing, and other prognostic factors. Your general allogeneic SCT may offer the best chance of a long-
health, current symptoms, and side effects will also lasting remission.
be noted. This can help to decide if you need and can
tolerate more intensive treatment for consolidation. The second option is to stay on the multiagent
chemotherapy regimen and TKI. This option is

64
suggested if a well-matched donor for the SCT has Staying on treatment with a TKI is a key part of
not been found. This may also be a good option if your maintenance therapy. Most maintenance regimens
doctor thinks an allogeneic SCT is too intense for you. include weekly methotrexate and daily 6-MP.
Often, monthly pulses of vincristine and a steroid
Consolidation therapy may include combinations of (prednisone or dexamethasone) are also given. A TKI
drugs similar to those used for induction. A TKI should such as imatinib or dasatinib should be added to the
be added to the consolidation therapy regimen for all maintenance regimen your doctor plans for you.
patients with Ph-positive ALL. Imatinib and dasatinib
are the main TKIs used for this phase. Staying on After consolidation with an allogeneic SCT,
treatment with a TKI can help keep ALL from coming maintenance therapy with a TKI is often
back after a complete remission. recommended. The TKI may be given alone. Or, other
drugs may also be given if side effects arent too
Often, chemotherapy drugs are given in higher severe.
(intensified) doses during consolidation. CNS
preventive treatment can also be given throughout this Methotrexate and 6-MP can affect the liver and lower
phase of treatment. Consolidation therapy may last the bone marrows ability to make new blood cells.
several months. How long it lasts and the total number These side effects can be severe and hard to tolerate.
of cycles varies based on the regimen used. The full If needed, lower doses of these drugs may be given
treatment regimen should be followed all the way to lessen the side effects.
through consolidation and to the end of maintenance.
Maintenance therapy drugs are often given in lower
If you are age 65 or older, or you have other doses and cause fewer side effects. CNS preventive
serious health problems, there are two main treatment can also be given throughout this treatment
options to choose from. A key part of both options phase. Maintenance therapy is given for about two
is to continue treatment with a TKI. Imatinib and to three years. But, the total length varies based
dasatinib are the main TKIs that may be used. The on the regimen used. Adult regimens tend to give
first option is to keep taking the TKI with or without maintenance therapy for a shorter amount of time
steroids such as prednisone or dexamethasone. The than pediatric-inspired regimens.
second option is to keep taking the TKI with or without
chemotherapy.
Maintenance therapy options Next steps:

The third phase of ALL treatment is called
maintenance. This phase is started after you finish After completing consolidation and
consolidation therapy. Maintenance therapy is
maintenance therapy, see Chart 5.5
given to keep up (maintain) the good results of prior
treatments. The goal is to prevent a relapse after on page 66 for follow-up testing.
induction and consolidation therapy. A relapse is
when leukemia cells come back after a complete
remission.

65
3
5 DCIS
Treatment guide Genetic
Follow-up
counseling
after|treatment
Treatmentfor ALL
5.5 Follow-up after treatment for ALL
Chart 5.5 Follow-up testing after treatment
Year Tests Timing
Physical exam and CBC with differential Once a month

Liver function tests Every 2 months until normal
Lumbar puncture As needed
Year 1 Echocardiogram As needed
Bone marrow aspiration As needed
If bone marrow aspiration is done, other tests may include:
As needed
Flow cytometry, cytogenetic testing, FISH, and PCR
Physical exam, including testicular exam Every 3 months
Year 2
CBC with differential Every 3 months
Physical exam, including testicular exam Every 6 months or as needed
Year 3+
CBC with differential Every 6 months or as needed
Chart 5.5 shows the tests that are recommended Follow-up tests
after completing the entire treatment regimen,
including induction, consolidation, and maintenance. The suggested schedule of follow-up tests is shown
Follow-up tests are given after treatment to check in Chart 5.5. Many of the tests used to diagnose ALL
how well treatment worked. and plan treatment are repeated during follow-up.
It is important for treatment to kill all of the leukemia During the first year of follow-up, a physical exam
cells and keep them away. Doctors use follow-up should be done once a month. The physical exam
tests to look for signs of cancer return (relapse) after gives your doctor an idea about your general health.
treatment. These tests also check how well your For males, it should include a testicular exam.
organs and body systems are working. This is needed
since ALL and its treatment can cause much damage. A CBC with differential should also be done once a
month during the first year of follow-up. This test will
show if there is normal number of each type of blood
cell.

66
5 Treatment guide Follow-up after treatment for ALL
Liver function tests will be done to check how well

your liver is working. Some ALL treatments can
damage the liver and cause abnormal liver function
Next steps:
test results. But, this is usually temporary and should
go away over time. If follow-up tests show ALL has come
back, more treatment is needed. For
A lumbar puncture removes a sample of spinal fluid
for testing. (See page 22 for more details). This test relapsed Ph-negative ALL, see Chart
may be used to check for a CNS relapse. A CNS 5.6.1 on page 68. For relapsed Ph-
relapse is when leukemia cells come back after
treatment and are found in the spinal fluid.
positive ALL, see Chart 5.6.2 on page
70.
An echocardiogram is an imaging test that shows how
well your heart is working. Doctors use this test to
check for signs of heart damage that may be caused
by ALL treatments.
A bone marrow aspiration may also be done at certain

times during the first year of follow-up. When this test
is done, your doctor may want to perform other lab
tests on the bone marrow sample. This may include
flow cytometry, cytogenetic testing, FISH, and PCR.
See Part 2 on page 14 to read more about each type
of test for ALL.
Follow-up tests are given less often during the second

and third years of follow-up. During the second year
of follow-up, tests are recommended once every three
months. And during the third year of follow-up, tests
are only recommended once every six months or as
needed.

67
3
5 DCIS
Relapsed
counseling
and refractory
| Treatment
ALL
5.6 Relapsed and refractory ALL
Chart 5.6.1 Treatment for relapsed or refractory Ph-negative ALL
Status Treatment options
Clinical trial,
Induction regimen not used before,

Refractory ALL
or Consider induction regimen used before if relapse is >3 years from diagnosis,
Relapsed ALL
Chemotherapy regimen for relapsed or refractory ALL, or
Allogeneic SCT
Chemotherapy regimens for relapsed or refractory Ph-negative ALL:

Blinatumomab for B-cell ALL
Regimens with cytarabine
Combination regimens with alkylating agents
Nelarabine for T-cell ALL
Augmented hyper-CVAD regimen
VSLI (vincristine sulfate liposome injection)
Regimens with clofarabine for B-cell ALL
Chart 5.6.1 shows the treatment options for Treatment options

relapsed or refractory Ph-negative ALL. Ph-
negative means the leukemia cells do not have the Your doctor will look at a number of factors unique
Philadelphia chromosome. to you to decide which treatment is the best choice.
Some factors include your age, general health,
A relapse is when leukemia cells come back after symptoms, and side effects. This helps your doctor
a complete remission. Refractory means that the to know if you are healthy enough to receive strong
leukemia cells didnt respond to treatment. ALL that treatments. How well prior treatment worked and how
isnt in complete remission after induction therapy long the treatment response lasted may also affect
is called refractory ALL. (See page 39 to read more which option is best.
about treatment responses.) Similar treatments are
used for relapsed ALL and refractory ALL. There are several treatment options to choose
from. But, any treatment given should include

68
5 Treatment guide Relapsed and refractory ALL
CNS preventive treatment. The options for treating of vincristine. This allows doctors to give higher doses
relapsed and refractory ALL are described next. of the drug without increasing side effects.
Treatment within a clinical trial is preferred if one is Another option for patients with B-cell ALL is to have
open and is the right fit for you. A clinical trial is a a regimen that includes clofarabine. Clofarabine
type of research that studies how safe and helpful a is approved for patients aged 21 or younger. But,
treatment is. If you arent able to join a clinical trial, adults may also benefit from regimens with this
there are a few other choices. chemotherapy drug.
A second option is to have a different induction An allogeneic SCT is also an option to consider if a
regimen than you had before. ALL that relapses matched donor has been found. In this case, your
more than three years after diagnosis is called a late doctor will assess if you are healthy enough to have
relapse. For AYAs with a late relapse, treatment with an allogenic SCT. Some patients may not be able to
the same induction regimen used before is an option tolerate this intensive treatment. This is especially
to consider. true for older adults who may have other health
problems.
Another option is to have chemotherapy for relapsed
or refractory ALL. There are many drugs and drug If ALL relapses after an initial allogeneic SCT, a
combinations to choose from. These are listed in the second allogeneic SCT is an option. Or your doctor
bottom of Chart 5.6.1. Blinatumomab is the preferred may consider a donor lymphocyte infusion. For this
option for B-cell ALL. Blinatumomab is a type of treatment, you will be given white blood cells called
targeted therapy called a monoclonal antibody. It uses lymphocytes from the same donor used for the SCT.
the immune system to help kill leukemia cells. (See
page 41 for details.)
Combination regimens that include cytarabine or an

alkylating agent such as ifosfamide are also options.
An alkylating agent is a type of chemotherapy drug
that directly damages the DNA in leukemia cells.
Nelarabine is an option for patients with T-cell ALL.
Augmented hyper-CVAD is an intense chemotherapy

regimen that may be used for relapsed or refractory
ALL. It uses many drugs and gives some in
higher (intensified) doses. This regimen includes
cyclophosphamide, vincristine, doxorubicin,
dexamethasone, pegaspargase, methotrexate, and
cytarabine.
VSLI is a form of the chemotherapy drug called

vincristine. VSLI has a special coating around it called
a liposome. The coating helps to limit the side effects

69
Chart 5.6.2 Treatment for relapsed or refractory Ph-positive ALL
Tests Treatment options
Clinical trial,
TKI alone,
Consider BCR-ABL
TKI chemotherapy,
gene mutation testing
TKI corticosteroids, or
Allogeneic SCT
TKIs and chemotherapy for relapsed or refractory Ph-positive ALL:

Dasatinib
Ponatinib
Imatinib
Nilotinib
Any TKI above + induction chemotherapy regimen not used before
If no response to TKIs, consider chemotherapy regimens for relapsed
or refractory Ph-negative ALL
Chart 5.6.2 shows the treatment options for Tests

relapsed or refractory Ph-positive ALL. Ph-positive
means the leukemia cells have the Philadelphia Before starting treatment, BCR-ABL gene mutation
chromosome. testing should be done. This test checks for changes
(mutations) in the BCR-ABL fusion gene that affect
A relapse is when leukemia cells come back after how well certain TKIs work. Each TKI drug works in
a complete remission. Refractory means that the a slightly different way. One TKI drug may be able
leukemia cells didnt respond to treatment. ALL that to work against a mutation that another TKI cant.
isnt in complete remission after induction therapy Knowing which mutations the BCR-ABL gene has will
is called refractory ALL. (See page 39 to read more help your doctor choose which TKI is best for you.
about treatment responses.) Similar treatments are
used for relapsed ALL and refractory ALL. Along with the mutation testing results, your doctor
will look at other factors to help plan treatment. Some
factors include your age, general health, symptoms,

70
and side effects. This helps your doctor to know if you An allogeneic SCT is also an option if you are healthy
are healthy enough to receive strong treatments. enough and a well-matched donor has been found.
Some patients may not be able to tolerate this
intensive treatment. This is especially true for older
Treatment options adults who may have other health problems.
There are several treatment options to choose If ALL relapses after the first allogeneic SCT, a
from. But, any treatment given should include second allogeneic SCT is an option. Or your doctor
CNS preventive treatment. The options for treating may consider a donor lymphocyte infusion. For this
relapsed and refractory ALL are described next. treatment, you are given white blood cells called
lymphocytes from the same donor used for the SCT.
Treatment within a clinical trial is preferred if one is
open and is the right fit for you. A clinical trial is a
type of research that studies how safe and helpful a
treatment is. If you arent able to join a clinical trial,
there are a few other choices.
A second option is to receive a different TKI than

you had during induction therapy. Many patients with
Ph-positive ALL receive imatinib during induction
therapy. TKI options for relapsed or refractory ALL are
dasatinib, ponatinib, imatinib, and nilotinib. The first
three TKIs listed are preferred over nilotinib.
The TKI may be given alone. Or, it may be

combined with multiagent chemotherapy or with a
corticosteroid. Prednisone and dexamethasone are
the main steroids that may be used. If combined with
chemotherapy, an induction regimen other than the
one you had before can be used.
Some older adults may not be able to tolerate

multiagent chemotherapy. Steroids can be easier
to take than chemotherapy. Thus, treatment with a
TKI and steroids may be the best choice for some
patients.
If ALL doesnt respond to treatment with TKIs, then

the regimens for relapsed or refractory Ph-negative
ALL may be tried. See Chart 5.6.1 on page 68.

71
3
5 DCIS
Notes
counseling | Treatment
My notes

72
6
Making treatment decisions

73
6 Making treatment
decisions
75 Where to get treated
75 Its your choice
76 Questions to ask your doctors
80 Weighing your options
82 Websites and resources
82 Review
Having cancer can feel very stressful.

While absorbing the fact that you
have cancer, you must also learn
about tests and treatments. And,
the time you have to decide on a
treatment plan may feel short. Parts
1 through 5 described the test and
treatment options recommended by
NCCN experts. These options are
based on science and agreement
among NCCN experts. Part 6 aims
to help you make decisions that are
in line with your beliefs, wishes, and
values.

74
6 Making treatment decisions Where to get treated | It's your choice
Where to get treated Its your choice

Treatment for ALL is very complex and intense. The role patients want in choosing their treatment
NCCN experts recommend that patients receive differs. You may feel uneasy about making treatment
treatment in a specialized cancer center with decisions. This may be due to a high level of stress. It
expertise in the management of ALL. may be hard to hear or know what others are saying.
Stress, pain, and medicines can limit your ability to
Receiving treatment in a specialized cancer center, make good decisions. You may feel uneasy because
such as an academic center, is important and you dont know much about cancer. You may have
beneficial for many reasons. You will be cared for by a never heard the words used to describe cancer, tests,
multidisciplinary team of experts who have advanced or treatments. Likewise, you may think that your
knowledge and experience in caring for people with judgment isnt any better than your doctors.
ALL. They can also offer you the newest and latest
treatments being studied in clinical trials as well as Letting others decide which option is best may make
current standard treatments. you feel more at ease. But, whom do you want to
make the decisions? You may rely on your doctors
A multidisciplinary team is a team of health alone to make the right decisions. However, your
professionals who are experts in different areas of doctors may not tell you which to choose if you have
cancer care. ALL is not common in adults. Therefore, multiple good options. You can also have loved
it is important to find a cancer center and doctor ones help. They can gather information, speak on
with experience in treating ALL in adults. An adult your behalf, and share in decision-making with your
hematologist/oncologist is a doctor who is an expert doctors. Even if others decide which treatment you
in treating blood cancers in adults. will receive, you still have to agree by signing a
consent form.
Patients who are 15 to 39 years of agecalled
AYAs (adolescents and young adults)may also On the other hand, you may want to take the lead
have a pediatric oncologist on their treatment team. or share in decision-making. Most patients do. In
A pediatric oncologist is a doctor who is an expert in shared decision-making, you and your doctors share
treating cancer in children. This is important because information, weigh the options, and agree on a
the treatments recommended for AYAs are based on treatment plan. Your doctors know the science behind
regimens designed for children. your plan but you know your concerns and goals. By
working together, you are likely to get a higher quality
AYAs may also want to consider treatment in a of care and be more satisfied. Youll likely get the
childrens cancer center or a center that has a treatment you want, at the place you want, and by the
dedicated AYA cancer program. For more detailed doctors you want.
information specifically for AYAs with cancer, see
the NCCN Guidelines for Patients: Caring for
Adolescents and Young Adults, available for free at
www.nccn.org/patients.

75
6 Making treatment decisions Questions to ask your doctors
Questions to ask your doctors

You will likely meet with experts from different fields of medicine. Strive to have helpful talks with
each person. Prepare questions before your visit and ask questions if the person isnt clear. You can
also record your talks and get copies of your medical records. It may be helpful to have your spouse,
partner, or a friend with you at these visits. A patient advocate or navigator might also be able to come.
They can help to ask questions and remember what was said. Some suggested questions to ask your
doctors are listed on the next pages.
Whats my diagnosis and prognosis?

Its important to know that there are different types of cancer. Cancer can greatly differ even when
people have a tumor in the same organ. Based on your test results, your doctors can tell you which
type of cancer you have. He or she can also give a prognosis. A prognosis is a prediction of the pattern
and outcome of a disease. Knowing the prognosis may affect what you decide about treatment.
1. Where did the cancer start? In what type of cell?
2. Is this cancer common?
3. Is this a fast- or slow-growing leukemia?
4. What is the ALL cell subtype and cytogenetic subtype? What does this mean for me and my
treatment options?
5. How often will I have bone marrow tests?
6. How often will I have spinal fluid tests?
7. What other test results are important to know?
8. How often are these tests wrong?
9. Would you give me a copy of the pathology report and other test results?
10. Can the cancer be cured? If not, how well can treatment stop the cancer from growing?

76
What are my options?

There is no single treatment practice that is best for all patients. There is often more than one
treatment option along with clinical trial options. Your doctor will review your test results and
recommend treatment options.
1. What will happen if I do nothing?
2. Can I just carefully monitor the cancer?
3. Do you consult NCCN recommendations when considering options?
4. Are you suggesting options other than what NCCN recommends? If yes, why?
5. Do your suggested options include clinical trials? Please explain why. What kinds of treatments
would the clinical trial involve? Is it specifically for people my age?
6. How do my age, health, and other factors affect my options?
7. Which option is proven to work best?
8. What are the benefits of each option? Does any option offer a cure? Are my chances any better
for one option than another? Less time-consuming? Less expensive?
9. What are the risks of each option? What are possible complications? What are the rare and
common side effects? Short-lived and long-lasting side effects? Serious or mild side effects?
Other risks?
10. What can be done to prevent or relieve the side effects of treatment?
11. Are there supportive services that I can get involved in? Support groups?

77
What does each option require of me?

Many patients consider how each option will practically affect their lives. This information may be
important because you have family, jobs, and other duties to take care of. You also may be concerned
about getting the help you need. If you have more than one option, choosing the option that is the
least taxing may be important to you.
1. Will I have to go to the hospital or elsewhere? How often? How long is each visit?
2. Do I have a choice of when to begin treatment? Can I choose the days and times of treatment?
3. How do I prepare for treatment? Do I have to stop taking any of my medicines? Are there foods I
will have to avoid?
4. Should I bring someone with me when I get treated?
5. Will the treatment hurt?
6. How much will the treatment cost me? What does my insurance cover? Does this differ if I have
treatment on a clinical trial?
7. Will I miss work or school? Will I be able to drive?
8. Is home care after treatment needed? If yes, what type?
9. How soon will I be able to manage my own health?
10. When will I be able to return to my normal activities?

78
What is your experience?

More and more research is finding that patients treated by more experienced doctors have better
results. It is important to learn if a doctor is an expert in the cancer treatment he or she is offering.
1. Are you board certified? If yes, in what area?
2. How much experience do you have in treating ALL?
3. How many patients like me have you treated? How many of them were my age?
4. How many treatments or procedures like the one youre suggesting have you done?
5. Is this treatment a major part of your practice?
6. How many of your patients have had complications?
7. Are you involved in any clinical trials for the treatment of ALL? For people my age?
8. Does your hospital have a program specifically for people my age with cancer?

79
6 Making treatment decisions Weighing your options
Weighing your options

Deciding which option is best can be hard. Doctors
from different fields of medicine may have different
opinions on which option is best for you. This can be
very confusing. Your spouse or partner may disagree
with which option you want. This can be stressful. In
some cases, one option hasnt been shown to work
better than another, so science isnt helpful. Some
ways to decide on treatment are discussed next.
2nd opinion
The time around a cancer diagnosis can be very
stressful. People with cancer often want to start
treatment as soon as possible. They want to make
the cancer go away before it spreads farther. While
cancer cant be ignored, there is time to think about your options. Choosing your cancer treatment is a
and choose which option is best for you. very important decision. It can affect your length and
quality of life.
You may wish to have another doctor review your test
results and suggest a treatment plan. This is called Support groups
getting a 2nd opinion. You may completely trust your Besides talking to health experts, it may help to talk
doctor, but a 2nd opinion on which option is best can to patients who have walked in your shoes. Support
help. groups often consist of people at different stages of
treatment. Some may be in the process of deciding
Copies of all of the test results need to be sent to while others may be finished with treatment. At
the doctor giving the 2nd opinion. Some people feel support groups, you can ask questions and hear
uneasy asking for copies from their doctors. However, about the experiences of other people with ALL.
a 2nd opinion is a normal part of cancer care.
Compare benefits and downsides
When doctors have cancer, most will talk with more Every option has benefits and downsides. Consider
than one doctor before choosing their treatment. these when deciding which option is best for you.
What's more, some health plans require a 2nd opinion. Talking to others can help identify benefits and
If your health plan doesnt cover the cost of a 2nd downsides you havent thought of. Scoring each
opinion, you have the choice of paying for it yourself. factor from 0 to 10 can also help since some factors
may be more important to you than others.
If the two opinions are the same, you may feel more
at peace about the treatment you accept to have.
If the two opinions differ, think about getting a 3rd
opinion. A 3rd opinion may help you decide between

80
6 Making treatment decisions Notes
My notes

81
6 Making treatment decisions Websites and resources | Review
Websites and resources The Samfund

www.thesamfund.org
American Cancer Society
www.cancer.org/cancer/leukemia- The Ulman Cancer Fund for Young Adults
acutelymphocyticallinadults/index www.ulmanfund.org
www.cancer.org/Treatment/ Critical Mass

FindingandPayingforTreatment/index www.criticalmass.org
National Cancer Institute The LIVESTRONG Foundation

www.cancer.gov/types/leukemia www.livestrong.org/we-can-help/fertility-services/
National Coalition for Cancer Survivorship

www.canceradvocacy.org/toolbox
Review
NCCN
www.nccn.org/patients/resources/life_with_ Shared decision-making is a process in which
cancer/default.aspx you and your doctors plan treatment together.
Asking your doctors questions is vital to

Leukemia and Lymphoma Society
getting the information you need to make
www.lls.org/leukemia/acute-lymphoblastic-
informed decisions.
leukemia
Getting a 2nd opinion, attending support
Resources for AYAs groups, and comparing benefits and
Cancer.Net downsides may help you decide which
www.cancer.net/navigating-cancer-care/young- treatment is best for you.
adults/resources-young-adults
National Cancer Institute

www.cancer.gov/types/aya/psychosocial-
challenges-cancer
www.cancer.gov/types/aya
Stupid Cancer
www.stupidcancer.org

82
Glossary
Dictionary
Acronyms

83
Glossary Dictionary
Dictionary
acute lymphoblastic leukemia (ALL) blood cell count
A fast-growing cancer that causes too many immature white The number of blood cells in a sample of blood.
blood cells called lymphoblasts to be made.
blood chemistry profile
adolescents and young adults (AYAs) A test that measures the amount of chemicals in the blood
Patients who are 15 to 39 years of age. to look for signs of disease and check how well organs are
working.
allogeneic stem cell transplant (SCT)
A treatment in which the patient receives immature blood- blood stem cell
forming cells (blood stem cells) from another person to An immature cell from which all other types of blood cells are
replace damaged or diseased cells in the bone marrow. made.
anesthesia bloodstream
Loss of feeling with or without loss of wakefulness caused by Blood that flows throughout the body in small tubes called
drugs. blood vessels.
anthracycline B-lymphocyte
A cancer drug that damages and disrupts the making of DNA One of two main types of white blood cells called
in cells. lymphocytes that help protect the body from infection and
disease.
B-cell
One of two main types of white blood cells called bone marrow
lymphocytes that help protect the body from infection and The soft, sponge-like tissue in the center of most bones
disease. Also called B-lymphocyte. where blood cells are made.
B-cell ALL bone marrow aspiration

A fast-growing (acute) blood cancer (leukemia) that starts in The removal of a small amount of liquid bone marrow (soft
a B-lymphoblastan immature cell that normally becomes a tissue in the center of most bones where blood cells are
mature white blood cell called a B-cell or B-lymphocyte. made) to test for disease.
BCR-ABL fusion gene bone marrow biopsy

An abnormal set of coded instructions for controlling cells The removal of a small amount of solid bone and bone
that is formed when the BCR gene and ABL gene join (fuse) marrow (the soft tissue in the center of most bones where
together on the Philadelphia chromosome. blood cells are made) to test for disease.
BCR-ABL protein cell assessment

An abnormal protein that is made by the BCR-ABL fusion Use of a microscope and special dyes to examine the
gene and causes too many abnormal white blood cells physical features of cells in a sample of blood or tissue
(leukemia cells) to be made. removed from your body. Also called morphologic
assessment.
biopsy
Removal of small amounts of tissue from the body to be cell subtype
tested for disease. Smaller groups that leukemia cells are classified into based
on the specific type of lymphocyte affected.
blast cell
An immature blood cell. central nervous system (CNS)
The brain and the spinal cordthe bundle of nerves that
runs from the base of the skull down the back.

84
Glossary Dictionary
central nervous system (CNS) disease corticosteroid

Leukemia cells in the fluid around the brain and spinal cord, A drug used to reduce redness, swelling, and pain, but also
which make up the central nervous system. to kill leukemia cells. Also called steroid.
central nervous system (CNS) preventive treatment cranial irradiation

Treatment given to keep leukemia cells from spreading to Treatment with high-energy rays (radiation) directed at the
the fluid around the brain and spinal cord. Also called CNS brain.
prophylaxis.
cycle
central venous line Days of treatment followed by days of rest.
A thin, flexible tube that is inserted into a vein to give
medicine or take a sample of blood. Also called central line
cytogenetic subtype
Smaller groups a type of cancer is classified into based on
or catheter.
abnormal changes in the chromosomes (long strands of
cerebrospinal fluid coded instructions) of the cancer cells.
The fluid that surrounds the brain and spinal cord. Also called
spinal fluid.
cytogenetic testing
A test that uses a microscope to examine a cells
chemotherapy chromosomes.
Drugs that kill fast-growing cells, including cancer cells and
normal cells.
deoxyribonucleic acid (DNA)
A chain of chemicals in cells that contains coded instructions
chromosomes for making and controlling cells.
Long strands of coded instructions in cells for making and
controlling cells.
diagnose
To confirm or identify a disease or health condition.
clinical trial
Research on a test or treatment to assess its safety or how
differential
Measurement of the different types of white blood cells
well it works.
present in a blood sample.
combination regimen
The use of two or more drugs.
donor
A person who gives their organs, tissues, or cells to another
complete blood count (CBC) person.
A test of the number of blood cells in a sample.
echocardiogram
complete remission A test that uses sound waves to make pictures of the heart.
No leukemia cells are found in the blood or bone marrow and
all signs and symptoms of the cancer are gone.
fatigue
Severe tiredness despite getting enough sleep that limits
computed tomography (CT) scan ones ability to function.
A test that uses x-rays from many angles to make a picture
of the inside of the body.
flow cytometry
A test that looks at certain substances on the surface of cells
consolidation to identify the type of cells present.
The second round (phase) of treatment that is given when
leukemia cells are no longer seen in the blood or bone
fluorescence in situ hybridization (FISH)
A lab test that uses special dyes to look for abnormal
marrow. Also called intensification or consolidation therapy.
changes in a cells genes (coded instructions for controlling
contrast cells) and chromosomes (long strands of genes).
A dye put into your body to make clearer pictures during
imaging tests.

85
Glossary Dictionary
follow-up test immunophenotyping

Tests done after the start of treatment to check how well The process of identifying the specific type of cells present
treatment is working. based on the unique set of proteins on the surface of the
cells.
fusion gene
A gene that is made by joining parts of two separate genes. induction
The first round (phase) of treatment given to rid the body of
gene leukemia cells. Also called remission induction or induction
A set of coded instructions in cells needed to make new cells
therapy.
and control how cells behave.
inflammation
gene mutation Redness, heat, pain, and swelling caused by illness or injury.
Abnormal change in the coded instructions in cells for
making and controlling cells. intensification
The second round (phase) of treatment that is given when
good risk feature leukemia cells are no longer seen in the blood or bone
Something linked with a lower chance (risk) that cancer will
marrow. Also called consolidation or intensification therapy.
come back after treatment.
intestine
graft-versus-host disease (GVHD) The organ that food passes through after leaving the
A disease that occurs when transplanted stem cells attack a
stomach.
patients normal cells.
intrathecal (IT) chemotherapy
graft-versus-leukemia (GVL) effect Cancer drugs that are injected into the fluid that surrounds
An attack on cancer cells by transplanted blood stem cells.
the brain and spinal cordthe bundle of nerves that runs
growth factor from the base of the skull down the back.
A substance that helps new blood cells to be made.
intravenous (IV)
human leukocyte antigen (HLA) Given by a needle or tube inserted into a vein.
Special proteins on the surface of cells that help the body to
kidneys
tell its own cells apart from foreign cells.
A pair of organs that filter blood and remove waste from the
human leukocyte antigen (HLA) type body through urine.
The unique set of proteins on the surface of cells that help
leukemia
the body to tell its own cells apart from foreign cells.
A type of cancer that starts in blood-forming cells in the bone
human leukocyte antigen (HLA) typing marrowthe soft, sponge-like tissue in the center of most
A blood test that finds a persons HLA typethe unique set bones where blood cells are made.
of proteins on the surface of cells that help the body to tell its
leukemia cell
own cells apart from foreign cells.
Abnormal, immature white blood cell that grows and divides
imaging test all the time without control.
A test that makes pictures (images) of the inside of the body.
liver
immune system Organ that removes waste from the blood and helps to digest
The bodys natural defense against infection and disease. food.
immunophenotype liver function test

The unique set and pattern of proteins on the surface of Test that measures chemicals in the blood that are made or
white blood cells that can be used to identify the type of cell. processed by the liver.

86
Glossary Dictionary
local anesthesia multidisciplinary

A controlled loss of feeling in a small area of the body Includes many doctors and other health care professionals
caused by drugs. who are experts in different areas of cancer care.
lumbar puncture mutation

A procedure in which a thin needle is inserted between the An abnormal change.
bones of the spine to remove a sample of spinal fluid or give
drugs into the spinal fluid.
pathologist
A doctor whos an expert in testing cells and tissue to find
lymph node disease.
A small group of disease-fighting cells.
pediatric-inspired
lymphatic system Based on treatment designed for or given to children.
A network of organs and tissues in the body that collects
and transports a fluid (lymph) and fights germs. This system
pediatric protocol
A detailed plan of a medical treatment for children.
includes the bone marrow, lymph nodes, lymph vessels,
thymus, and spleen. pediatric regimen
A treatment plan that specifies the drug(s), dose, and
lymphoblast
schedule for a course of treatment designed for or given to
An immature cell that becomes a mature white blood cell
children.
called a lymphocyte.
lymphoblastic lymphoma Philadelphia chromosome

An abnormal, short chromosome 22 that is formed when
A fast-growing cancer that starts in the lymphatic system and
parts of chromosomes 9 and 22 switch with each other. Also
causes too many lymphoblasts to build up in lymph nodes or
called Ph chromosome.
other parts of the lymph system.
lymphocyte Ph-negative ALL

The leukemia cells do not contain the abnormal Philadelphia
A type of white blood cell that helps protect the body from
chromosome.
infection and disease.
magnetic resonance imaging (MRI) scan Ph-positive ALL

The leukemia cells contain the abnormal Philadelphia
A test that uses radio waves and powerful magnets to make
chromosome.
pictures of the inside of the body.
maintenance physical exam

A review of the body by a health expert for signs of disease.
The third round (phase) of treatment that is given to keep up
(maintain) good treatment results. platelet
A type of blood cell that helps control bleeding.
microscope
A tool that uses lenses to see things the eyes cant. polymerase chain reaction (PCR)
A sensitive lab test that is used to look for abnormal changes
minimal residual disease (MRD)
in a cells genes (coded instructions for controlling cells) and
A very small amount of cancer cells left in the body after
chromosomes (long strands of genes).
treatment that cant be seen with a microscope.
monoclonal antibody poor risk feature

Something linked with a higher chance (risk) that cancer will
A type of immune system protein that is made in a lab and
come back after treatment.
can attach to a certain target, such as a substance on the
surface of cancer cells. positron emission tomography (PET) scan
A test that uses radioactive material to take pictures of the
multiagent chemotherapy
inside of the body.
The use of two or more cancer drugs.

87
Glossary Dictionary
postremission therapy spinal fluid

Treatment given after all signs and symptoms of cancer have The fluid that surrounds the brain and spinal cord. Also called
disappeared (called a remission) following initial treatment. cerebrospinal fluid.
prognosis spleen
The likely or expected course, pattern, and outcome of a An organ to the left of the stomach that helps protect the
disease based on tests. body from disease.
prognostic factor stem cell transplant (SCT)

Something that affects and helps predict the likely outcome Treatment that replaces damaged or diseased cells in the
of a disease. bone marrowsoft tissue in the center of bones where blood
cells are madewith healthy blood-forming cells called blood
protocol stem cells.
A detailed plan of a medical study, treatment, or procedure.
steroid
radiation therapy A drug used to reduce redness, swelling, and pain, but also
Use of high-energy rays to destroy cancer cells.
to kill leukemia cells. Also called corticosteroid
red blood cell subtype
A type of blood cell that carries oxygen from the lungs to the
Smaller groups that a type of cancer is divided into based on
rest of the body.
certain features of the cancer cells.
refractory supportive care
Disease that does not improve or go away in response to
Treatment for the symptoms or health conditions caused by
treatment.
cancer or cancer treatment.
regimen symptom
A treatment plan that specifies the drug(s), dose, and
A new or changed health problem a person experiences that
schedule for a course of treatment.
may indicate a disease.
relapse targeted therapy
The return of leukemia cells after a period of improvement.
Treatment with drugs that target a specific or unique feature
remission of cancer cells.
The signs and symptoms of cancer have disappeared as a
T-cell
result of treatment.
One of two main types of white blood cells called
remission induction lymphocytes that help protect the body from infection and
The first round (phase) of treatment that is given to rid the disease. Also called T-lymphocyte.
body of leukemia cells and make all signs and symptoms
T-cell ALL
of the cancer disappear. Also called induction or induction
A fast-growing (acute) blood cancer (leukemia) that starts in
therapy.
a T-lymphoblastan immature cell that normally becomes a
sedative mature white blood cell called a T-cell or T-lymphocyte.
A drug that helps a person to relax or go to sleep.
testicles
side effect Two egg-shaped glands found inside the sac between the
An unhealthy or unpleasant physical or emotional response legs of a man.
to treatment.
thymus
spinal cord A small organ in the upper, front part of the chest that is part
The bundle of nerves that runs from the base of the skull of the bodys disease-fighting system.
down the back and carries messages between the brain and
other parts of the body.

88
Glossary Dictionary
T-lymphocyte tyrosine kinase inhibitor (TKI)

One of two main types of white blood cells called A type of drug that targets and blocks the protein made by
lymphocytes that help protect the body from infection and the BCR-ABL gene so that it cant tell leukemia cells to grow.
disease. Also called T-cell.
U.S. Food and Drug Administration (FDA)
transfusion A federal government agency that regulates drugs and food.
Replacing lost blood with new blood.
uric acid
translocation A chemical that is made and released into the blood when
When pieces of two chromosomes (long strands of coded cells and other substances in the body break down.
instructions for controlling cells) break off and switch with
each other.
vaccine
A biological agent inserted into the body to prevent a
treatment response disease.
An outcome or improvement related to treatment.
vein
tumor lysis syndrome (TLS) A small tube that carries blood to the heart from anywhere in
A condition that occurs when many cancer cells die very the body.
quickly and release their contents into the blood, which can
damage the kidneys and other organs.
white blood cell
A type of blood cell that helps fight infections in the body.
tumor lysis syndrome (TLS) panel
A test that measures certain chemicals that are released into
the blood when cancer cells die.

89
Glossary Acronyms
Acronyms
6-MP MRI
6-mercaptopurine magnetic resonance imaging
ALL PCR
acute lymphoblastic leukemia polymerase chain reaction
AYA PET
adolescent and young adult positron emission tomography
CBC Ph-negative
complete blood count Philadelphia chromosome negative
CNS Ph-positive
central nervous system Philadelphia chromosome positive
CT SCT
computed tomography stem cell transplant
DNA TKI
deoxyribonucleic acid tyrosine kinase inhibitor
EBRT TLS
external beam radiation therapy tumor lysis syndrome
FDA VSLI
U.S. Food and Drug Administration vincristine sulfate liposome injection
FISH
fluorescence in situ hybridization
NCCN Abbreviations and Acronyms
GVHD
graft-versus-host disease NCCN
National Comprehensive Cancer Network
GVL
graft-versus-leukemia NCCN Patient Guidelines
HLA NCCN Guidelines for Patients
human leukocyte antigen
NCCN Guidelines
IT NCCN Clinical Practice Guidelines in Oncology
intrathecal
IV
intravenous
MRD
minimal residual disease

90
N C C N G U I D E L I N E S F O R PAT I E N T S
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View and download your free copy NCCN.org/patients

Order print copies Amazon.com (Search NCCN Guidelines for Patients)
Acute Lymphoblastic Leukemia Malignant Pleural Mesothelioma Non-Small Cell Lung Cancer
Caring for Adolescents and Melanoma Ovarian Cancer
Young Adults (AYA)* Multiple Myeloma Pancreatic Cancer
Chronic Lymphocytic Leukemia Myelodysplastic Syndromes Prostate Cancer
Chronic Myelogenous Leukemia Non-Hodgkins Lymphomas Soft Tissue Sarcoma
Colon Cancer Diffuse Large B-cell Lymphoma Stage 0 Breast Cancer
Esophageal Cancer Follicular Lymphoma
Stages I and II Breast Cancer
Mantle Cell Lymphoma
Hodgkin Lymphoma Stage III Breast Cancer
Mycosis Fungoides
Kidney Cancer Peripheral T-cell Lymphoma Stage IV Breast Cancer
Lung Cancer Screening
The NCCN Guidelines for Patients

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92
NCCN Panel Members
NCCN Panel Members for

Acute Lymphoblastic Leukemia
Joseph C. Alvarnas, MD/Co-Chair Daniel J. DeAngelo, MD, PhD Geoffrey L. Uy, MD
City of Hope Comprehensive Cancer Center Dana-Farber/Brigham and Womens Siteman Cancer Center at Barnes-
Cancer Center Jewish Hospital and Washington
Patrick A. Brown, MD/Co-Chair University School of Medicine
The Sidney Kimmel Comprehensive Olga Frankfurt, MD
Cancer Center at Johns Hopkins Robert H. Lurie Comprehensive Cancer Eunice S. Wang, MD
Center of Northwestern University Roswell Park Cancer Institute
Anjali Advani, MD
Case Comprehensive Cancer Center/ John P. Greer, MD Andrew D. Zelenetz, MD, PhD
University Hospitals Seidman Cancer Center Vanderbilt-Ingram Cancer Center Memorial Sloan Kettering Cancer
and Cleveland Clinic Taussig Cancer Institute Centerospital
Robert A. Johnson, MD, FACP
Patricia Aoun, MD, MPH St. Jude Childrens Research Hospital/
City of Hope Comprehensive Cancer Center The University of Tennessee NCCN Staff
Health Science Center
Karen Kuhn Ballen, MD Kristina M. Gregory, RN, MSN, OCN
Massachusetts General Hospital Hagop M. Kantarjian, MD Vice President/Clinical Information Operations
Cancer Center The University of Texas
MD Anderson Cancer Center
Dorothy A. Shead, MS
Stefan K. Barta, MD, MS, MRCP Director, Patient and Clinical Information
Fox Chase Cancer Center Rebecca B. Klisovic, MD Operations
The Ohio State University Comprehensive
Michael W. Boyer, MD Cancer Center - James Cancer Hospital
and Solove Research Institute Courtney Smith, PhD
Huntsman Cancer Institute
Oncology Scientist/Medical Writer
at the University of Utah
Gary Kupfer, MD
Patrick W. Burke, MD Yale Cancer Center/Smilow Cancer Hospital
University of Michigan
Comprehensive Cancer Center Mark Litzow, MD
Mayo Clinic Cancer Center
Ryan Cassaday, MD
Fred Hutchinson Cancer Research Center/ Arthur Liu, MD, PhD
Seattle Cancer Care Alliance University of Colorado Cancer Center
Januario E. Castro, MD Jai Park, MD

UC San Diego Moores Cancer Center Memorial Sloan Kettering Cancer Center
Peter F. Coccia, MD Arati V. Rao, MD

Fred & Pamela Buffett Cancer Center Duke Cancer Institute
Steven E. Coutre, MD Bijal Shah, MD

Stanford Cancer Institute Moffitt Cancer Center
Lloyd E. Damon, MD
UCSF Helen Diller Family
Comprehensive Cancer Center
For disclosures, visit www.nccn.org/about/disclosure.aspx.

93
NCCN Member Institutions
NCCN Member Institutions

Fred & Pamela Buffett Cancer Center The Sidney Kimmel Comprehensive Stanford Cancer Institute
Omaha, Nebraska Cancer Center at Johns Hopkins Stanford, California
800.999.5465 Baltimore, Maryland 877.668.7535
nebraskamed.com/cancer 410.955.8964 cancer.stanford.edu
hopkinskimmelcancercenter.org
Case Comprehensive Cancer Center/ University of Alabama at Birmingham
University Hospitals Seidman Robert H. Lurie Comprehensive Cancer Comprehensive Cancer Center
Cancer Center and Cleveland Clinic Center of Northwestern University Birmingham, Alabama
Taussig Cancer Institute Chicago, Illinois 800.822.0933
Cleveland, Ohio 866.587.4322 www3.ccc.uab.edu
800.641.2422 UH Seidman Cancer Center cancer.northwestern.edu
uhhospitals.org/seidman UC San Diego Moores Cancer Center
866.223.8100 CC Taussig Cancer Institute Mayo Clinic Cancer Center La Jolla, California
my.clevelandclinic.org/services/cancer Phoenix/Scottsdale, Arizona 858.657.7000
216.844.8797 Case CCC Jacksonville, Florida cancer.ucsd.edu
case.edu/cancer Rochester, Minnesota
800.446.2279 Arizona UCSF Helen Diller Family
City of Hope Comprehensive 904.953.0853 Florida Comprehensive Cancer Center
Cancer Center 507.538.3270 Minnesota San Francisco, California
Los Angeles, California mayoclinic.org/departments-centers/mayo- 800.689.8273
800.826.4673 clinic-cancer-center cancer.ucsf.edu
cityofhope.org
Memorial Sloan Kettering University of Colorado Cancer Center
Dana-Farber/Brigham and Cancer Center Aurora, Colorado
Womens Cancer Center New York, New York 720.848.0300
Massachusetts General Hospital 800.525.2225 coloradocancercenter.org
mskcc.org
Cancer Center
Boston, Massachusetts University of Michigan
877.332.4294 Moffitt Cancer Center Comprehensive Cancer Center
dfbwcc.org Tampa, Florida Ann Arbor, Michigan
massgeneral.org/cancer 800.456.3434 800.865.1125
moffitt.org mcancer.org
Duke Cancer Institute
Durham, North Carolina The Ohio State University The University of Texas
888.275.3853 Comprehensive Cancer Center - MD Anderson Cancer Center
dukecancerinstitute.org James Cancer Hospital and Houston, Texas
Solove Research Institute 800.392.1611
Fox Chase Cancer Center Columbus, Ohio mdanderson.org
Philadelphia, Pennsylvania 800.293.5066
888.369.2427 cancer.osu.edu Vanderbilt-Ingram Cancer Center
foxchase.org Nashville, Tennessee
Roswell Park Cancer Institute 800.811.8480
Huntsman Cancer Institute Buffalo, New York vicc.org
at the University of Utah 877.275.7724
Salt Lake City, Utah roswellpark.org University of Wisconsin
877.585.0303 Carbone Cancer Center
huntsmancancer.org Siteman Cancer Center at Barnes- Madison, Wisconsin
Jewish Hospital and Washington 608.265.1700
Fred Hutchinson Cancer University School of Medicine uwhealth.org/cancer
Research Center/ St. Louis, Missouri
Seattle Cancer Care Alliance 800.600.3606 Yale Cancer Center/
Seattle, Washington siteman.wustl.edu Smilow Cancer Hospital
206.288.7222 seattlecca.org New Haven, Connecticut
206.667.5000 fredhutch.org St. Jude Childrens Research Hospital/ 855.4.SMILOW
The University of Tennessee yalecancercenter.org
Health Science Center
Memphis, Tennessee
888.226.4343 stjude.org
901.683.0055 westclinic.com

94
Notes
My notes

95
Index
Index
adolescent and young adult (AYA) 28, 36, 46, 4853, targeted therapy 40, 41, 46, 58, 63, 69
5861, 69, 75 tyrosine kinase inhibitor (TKI) 40, 41, 58, 6065, 70, 71
BCR-ABL gene 20, 21, 40, 58, 63, 70
bone marrow 4, 69, 12, 15, 16, 1821, 24, 36, 37, 39, 42,
43, 45, 46, 50, 51, 54, 55, 58, 59, 6163, 6567
bone marrow aspiration 18, 24, 66, 67
bone marrow biopsy 18, 24
central nervous system (CNS) 3537, 44, 46, 5054,
5659, 61, 62, 65, 67, 69, 71
chemotherapy 3438, 40, 42, 43, 45, 46, 50, 5258,
6065, 6871
chromosome 8, 1921, 24, 27, 29, 30, 40, 48, 49, 52, 53,
5658, 60, 63, 64, 68, 70
clinical trial 33, 46, 49, 50, 54, 55, 58, 62, 63, 6871, 75
consolidation 37, 43, 46, 5153, 5557, 5961, 6366
follow-up 52, 53, 56, 57, 61, 6567
imaging test 23, 67
induction 37, 39, 46, 5066, 6871
intrathecal (IT) chemotherapy 35, 36, 50, 54, 58, 62
lumbar puncture 15, 22, 36, 50, 54, 58, 62, 66, 67
maintenance 36, 37, 46, 52, 53, 56, 57, 60, 61, 6466
multidisciplinary team 49, 75
older adult 28, 36, 48, 49, 5457, 6265, 69, 71
Philadelphia chromosome 20, 21, 27, 29, 40, 48, 49, 58,
63, 68, 70
protocol 36, 50
refractory 39, 48, 50, 51, 55, 58, 59, 63, 6870
regimen 34, 36, 40, 42, 46, 5071, 75
relapse 39, 48, 53, 57, 61, 6571
remission 37, 39, 48, 5068, 70
response 39, 40, 50, 51, 54, 55, 58, 59, 62, 63, 68, 70
side effect 16, 28, 33, 3638, 4046, 52, 53, 5557, 6065,
68, 69, 71
stem cell transplant (SCT) 36, 4244, 52, 53, 56, 57, 60,
61, 64, 65, 6871
subtype 27, 29, 30, 40, 49, 52, 56, 60, 64

96

Acute Lymphoblastic
Leukemia
Version 1.2016
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Guidelines for Patients. NCCN independently develops and distributes the NCCN Guidelines for Patients. Our industry supporters do
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NCCN Guidelines for Patients Version 1.2016

Available online at NCCN.org/patients

The National Comprehensive Cancer Network (NCCN) is a not-for-profit

This book focuses on the treatment of acute lymphoblastic leukemia. Key

NCCN Guidelines for Patients

Dorothy A. Shead, MS Lacey Marlow Susan Kidney

Supported by NCCN Foundation

National Comprehensive Cancer Network (NCCN)

2016 National Comprehensive Cancer Network, Inc. All rights reserved.

NCCN Guidelines for Patients

NCCN Guidelines for Patients

Making sense of medical

NCCN Guidelines for Patients

NCCN Guidelines for Patients

What are lymphoblasts?

Lymphoblasts are a type of very young white blood

The two main types of lymphocytes are

Most blood cells are made in the bone marrow. Bone

NCCN Guidelines for Patients

Bone marrow is the soft, sponge-like

Blood stem cell

A blood stem cell goes through

NCCN Guidelines for Patients

Figure 1.3 Human

Genes are coded instructions in cells

Illustration Copyright 2016 Nucleus Medical Media, All rights reserved.

NCCN Guidelines for Patients

Second, leukemia cells dont grow into mature

Normal cells grow and divide to make

Illustration Copyright 2016 Nucleus Medical Media, All rights reserved.

NCCN Guidelines for Patients

What are the symptoms of ALL?

Some common symptoms that may be caused by ALL

Severe tiredness (fatigue),

However, these symptoms may be caused by other

NCCN Guidelines for Patients

NCCN Guidelines for Patients

NCCN Guidelines for Patients

NCCN Guidelines for Patients

A medical history is needed for treatment planning.

NCCN Guidelines for Patients

Chart 2.1 Initial tests for diagnosis

Tests of blood or bone marrow needed for all patients

Cell assessment (morphologic assessment)

Chart 2.2 Tests for treatment planning

NCCN Guidelines for Patients

Physical exam Blood tests

A CBC with differential is given with other initial tests

NCCN Guidelines for Patients

NCCN Guidelines for Patients

Doctors use a bone marrow

NCCN Guidelines for Patients

ALL cells have a common pattern or signature of

Flow cytometry can identify the type of leukemia cells

Flow cytometry involves first adding a markera

NCCN Guidelines for Patients

Genetic tests chromosomes. This test can also be used to count

NCCN Guidelines for Patients

NCCN Guidelines for Patients

Doctors perform a lumbar

NCCN Guidelines for Patients

NCCN Guidelines for Patients