Acute Leukemia

Rakesh Biswas

MD, Professor, Department of Medicine,

People's College of Medical Sciences,
Bhanpur, Bhopal, India
 A 16 year old girl

Extreme pallor
gum bleeds, Purpura,With
Lymphadenopathy and
Hepatosplenomegaly
 Possible causes:

Investigations and treatment

Only a week later, D was ill
again, with a fever, severe
headache, and extreme
lethargy.
During a sunny spring weekend,
D would go outside to play, only
to return minutes later
exhausted, flopping herself onto
the sofa to rest
 Leukemia

Group of malignant disorders of the

hematopoietic tissues characteristically
associated with increased numbers of
white cells in the bone marrow and / or
peripheral blood
Once inside the van and on our
way out of the clinic parking lot,
she asked,

"Dad, what is leukemia?"

"Can I die from this?"

 Classification
Classified based on cell type involved
and the clinical course
1. Acute :
ALL
AML

2. Chronic :
CLL
CML
Subclassification

ALL
Common type( pre-B)
B-cell
T-cell
Undifferentiated
After the oncologist performed a
bone marrow aspiration to
confirm the diagnosis of
leukemia, we learned
specifically what type it was and
the count. "D had acute
lymphoblastic leukemia, early
pre-B cell.
Myelomono
AML
French-American-British (FAB) Classification

M0: Minimally differentiated leukemia

M1: Myeloblastic leukemia without maturation
M2: Myeloblastic leukemia with maturation
M3: Hypergranular promyelocytic leukemia
M4Eo: Variant: Increase in abnormal marrow
eosinophils
M4: Myelomonocytic leukemia
M5: Monocytic leukemia
M6: Erythroleukemia (DiGuglielmo's disease)
M7: Megakaryoblastic leukemia
Ref-Harrisons Principle of Internal Medicine
 CLL
B-cell: common
T-cell: rare
 CML
Ph +ve
Ph ve, BCR-abl +ve
Ph ve, BCR-abl -ve
Eosinophilic Leukemia

Ph: Philadelphia chromosome

BCR: Breakpoint cluster region; abl : Abelson oncogene
Acute Myeloid Leukemia
( AML)
Malignant transformation of a
myeloid precursor cell ;
usually occurs at a very early stage
of myeloid development

Rare in childhood & incidence

increases with age
 Etiology
Unknown / De-novo !! In majority

Predisposing factors:
Ionizing radiation exposure
Previous chemotherapy : alkylating agents
Occupational chemical exposure : benzene
Genetic factors: Downs Syndrome, Blooms,
Fanconis Anemia
Viral infection ( HTLV-1)
Immunological : hypogammaglobulinemia
Acquired hematological condition -Secondary
 Epidemiology
M>F

ALL which predominantly affects

younger individuals
AML adults and the elderly
Median age gp-65yrs

Geographical variation-none
 Clinical features
General :
Onset is abrupt & stormy
(usually present within 3 months)

Bone marrow failure

(anemia, infection ,bleeding)

Bone pain & tenderness

Specific:
M2 : Chloroma:-presents as a mass lesion
tumor of leukemic cells
M3 : DIC
M4/M5 : Infiltration of soft tissues,
gum infiltration, skin deposits ,Meningeal
involvement-headache, vomiting, eye
symptoms
Skin Infiltration with AML (Leukemia Cutis)
 Diagnosis
Blood count :
WBC usually elevated (50,000- 1,00,000
/ cmm ); may be normal or low;
often anemia & thrombocytopenia

Blood film : (as above)

Blast cells
P. Smear AML
 Bone marrow aspirate & trephine:
Hypercellular,
blast cells ( > 20%),
presence of Auer rods - AML type

Cytochemistry :
Special stains to differentiate AML
from ALL ;
Positivity with Sudan black &
Myeloperoxidase (MPO) in AML
 Jemshidi trephine &
Salah aspiration needle
Auer Rods in Leukemia cells
MPO (right) & Sudan black (left)
showing intense localised positivity
in blasts
 Confirmation:
Immunophenotyping
Molecular genetics
Cytogenetics: Chromosomal
abnormalities
Other Inv:

Coagulation screen,
fibrinogen,
D- dimer
RFT, LFT
LDH, Uric acid
Urine
CXR
ECG, ECHO
 Management
I. Supportive care :
Anemia red cell transfusion
Thrombocytopenia platelet
concentrates
Infection broad spectrum IV antibiotics
Hematopoietic growth factors :
GM-CSF, G-CSF

Barrier nursing
Indwelling central venous catheter
 Metabolic problems :
Monitoring hepatic / renal /
hematologic function;
Fluid & electrolyte balance, nutrition
Hyperuricemia- hydration, Allopurinol

Psychological support
The white blood cell count in her
peripheral blood was about
550,000.

Her bone marrow was packed

with leukemia blasts."
The next thing that occurred
was a procedure called
leukopheresis.

This procedure lasted 4 hours

and cut Ds white blood cell
(WBC) count in half--to about
250,000.
She was administered
chemotherapy immediately
following the leukopheresis
procedure.

The next day we learned that

the chemo had produced an
effect as well: The WBC had
halved again--125,000.
SPECIFIC THERAPHY:
Chemotherapy :

Induction: (4-6 wks)

vincristine, prednisone,
anthracycline, (idarubicin or
daunorubicin)
cyclophosphamide, and L-asparaginase
Consolidation: (multiple cycles of
intensive chemotherapy given over a 6 to 9
month period).

Cytosine arabinoside, high-dose

methotrexate, etoposide
anthracycline, (idarubicin or daunorubicin)
Maintenance phase:
(18 to 24 months).

LPs with intrathecal MTX every 3

months,

Monthly vincristine,

Daily 6-MP, and weekly MTX.

At day 29 of the induction
protocol D was declared to be in
complete remission.

We were all relieved with this

news.
Step two was the next phase of
treatment called consolidation
therapy.

This entailed multiple

combinations of drugs
administered on a rotational
basis (on various weeks) for the
next six months.
For instance, she would receive
an infusion of methotrexate for a
couple of days and then take 6-
MP by mouth for a week.

Another cycle included VM-26

(Teniposide) and Ara-C.
 Complete remission ( CR):
< 5% blast cells in normocellular bone marrow
Autologous BMT :
Can be curative in younger patient (< 40-50 yrs)
Exactly 5 months since her
diagnosis, and 16 weeks of
remission

"We're at the clinic. D has

relapsed. Her white count is
27,000."
The Consolidation protocol had
been dropped and replaced with
a new induction protocol.

After the bone marrow aspiration to

determine the extent of the leukemia
relapse, she was given doxirubicin,
vincristine and L-asparaginase.
For several days following Ds
discharge from the bone
marrow transplant unit, all of us
loaf around the house and
recuperate from our 90 day
marathon
the first 30 days representing
Ds' relapse and the induction
therapy to obtain a second
remission
Back in fighting form, D
proceeds directly to the final 30
days of the marathon--the
actual bone marrow transplant.

BMT patients are in a delicate

condition following discharge
Looking back, the nine weeks or
so--the post BMT discharge
period--was a sublime time for
us.

D was home and was feeling

pretty good.
As Ds hair began to grow
again, we rubbed her head
every night at the dinner table,
wondering what color it was
going to be or if it was going to
be curly or straight.

We never found out.

On Monday, March 1, 1999 we
went to clinic and waited for the
lab results.

The results came back as we

feared.

D had relapsed. Her white

count was 47,000. We were
devastated.
 III. PALLIATIVE THERAPHY
Chemo, RT, Blood product support
 Prognosis
Median survival without treatment is 5
weeks
30% 5-yr survival in younger patients with
chemotherapy
Disease which relapses during treatment
or soon after the end of treatment has a
poor prognosis
Poor prognostic factors

Increasing age
Male sex
High WBC count at diagnosis
CNS involvement at diagnosis
Cytogenetic abnormalities
Antecedent hematological
abnormalities (eg. MDS)
No complete remission
Two things that I will always
remember about D: She was a
collector of many things, trinket
boxes, key rings.

But she was first and foremost a

collector of "FRIENDS."
Among other things, she wrote:

"Hair loss is a side effect of

chemotherapy, and cancer is a
side effect of life."
 Summary;

Learning Points
THANK YOU