Acute

Lymphoblastic
Leukemia
Muhammad Fadhel
1410311044

Definition
Neoplastic disease which results from a
mutation in a single lymphoid progenitor
cell at one of several discrete stages of
development
B Cell or T Cell

Epidemiology
Most common childhood acute leukemia,
~80%
Incidence in adults ~20%
Bimodal distribution of occurrence:

Peak

at age 2-5
Second increased incidence after age 50

Pathogenesis

Acquired Genetic Change in Chromosome

Change

in number, ie ploidy
Change in structure

Translocations (most common)

Inversions
Deletions
Point mutations
Amplifications
Changes in normal means of cell differentiation, proliferation, and
survival

Mechanisms of Leukemia Induction

1 Activation of a protooncogene OR creation of

a fusion gene with
oncogenic properties
- Ph Chromosome t(9;22)

2 Loss or inactivation
of 1 tumor
suppressor gene
- p53 (p16 mutation)

Etiology

Unknown
? Genetic Predisposition

Increased incidence amongst monozygotic and dizygotic twins

Down Syndrome
Disorder with chromosomal fragility:
Fanconis anemia
Bloom Syndrome
Ataxia-Telangiectasia

? Infections
HTLV1 in T cell leukemia/lymphoma
EBV in mature B cell ALL
HIV in lymphoproliferative DO

Presentation

Nonspecific Symptoms
Fatigue/decreased

energy

Fever
Easy

bruising
Bleeding
Dyspnea
Dizziness
Infection

Joint, extremity pains

CNS involvement

Clinical Presentation

Physical Exam

Lab Abnormalities

Pallor

anemia

Ecchymoses

wbc

Petechiae
LAD
Hepatosplenomegaly

0.1 (20-40%) - >100 k

(10-16%)
Platelets usually
LD, uric acid
CXR: eval for thymic mass
CSF to eval for
involvement

vary

Diagnosis

Morphologic
French

American British Classification

L1: small uniform blasts (pediatric ALL)

L2: larger, more variable sized blasts (adult ALL)
L3: uniform cells with basophilic and sometimes
vacuolated cytoplasm (mature B cell ALL)

Immunophenotyping

From: Jabbour, E. et al. Adult Acute Lymphoblastic

Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527

Cytogenetic Abnormalities

From: Jabbour, E. et al. Adult Acute Lymphoblastic

Leukemia. Mayo Clinic Proc. 2005;80(11):1517-

Classification of ALL
Immunologic
Subtype

% of cases

FAB Subtype

Cytogenetic
Abnormalities

Pre-B ALL

75

L1, L2

t(9;22), t(4;11),
t(1;19)

T cell ALL

20

L1, L2

14q11 or 7q34

B cell ALL

L3

t(8;14), t(8;22),
t(2;8)

From: Harrisons Principles of Internal Medicine, 16th

ed. 2005. Chapter 97, Malignancies of lymphoid cells.

Differential Diagnosis
ITP
Aplastic Anemia
Infectious mononucleosis
Rheumatoid Arthritis
Rheumatic Fever
Collagen Vascular Disease

Treatment
1 Remission Induction
2 Intensification (Consolidation) Therapy
3 Maintenance Therapy
4 CNS Prophylaxis
5 Allogeneic Stem Cell Transplant

Treatment

Remission Induction
Goals:

restore normal hematopoiesis, induce a

complete remission rapidly in order to prevent
resistance to drugs
Standard induction regimen

4 or 5 drugs: vincristine, prednisone, anthracycline, Lasparaginase, +/- cyclophosphamide

Intensification
High

doses of multiple agents not used during

induction or re-administration of the induction regimen

Treatment

Maintenance Therapy
Daily

po 6MP, weekly MTX, monthly pulses of

vincristine and prednisone for 2-3 yrs

CNS Prophylaxis
Given

during induction and intensification

Intrathecal: MTX, Cytarabine, corticosteroids
Systemic: high dose mtx, cytarabine, L-asparaginase
+/- Cranial Irradiation

Treatment

Stem Cell Transplant

Done

during first CR
Indications:

Ph Chromosome
t(4;11) mutation
Poor initial response to induction therapy

Other
Adolescents

benefit significantly from pediatric ALL

regimens vs. adult regimens

Relapse & Prognosis

Relapse
Most

occur during treatment or within the first 2 years

Bone Marrow is the most common site
Poor prognostic factors in patients previously treated:

Relapse on therapy
Short initial remission after intense therapy
T-cell immunophenotype
Ph Chromosome
Circulating blasts
High leukocyte count at relapse

Prognosis
Overall better in children than in adults
In adults, worse outcomes with:

Increasing

age, >60
Increased wbc count at presentation