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?"

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

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

Malignant

(transformation
AML)
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 (50,0001,00,000
/ 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,

RFT, LFT
LDH,

Uric acid

Urine
CXR
ECG,

ECHO

D- dimer

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

She was administered

chemotherapy immediately
following the leukopheresis
procedure.

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,

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

For instance, she would receive

an infusion of methotrexate for a
couple of days and then take 6MP by mouth for a week.

 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

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

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

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.

Looking back, the nine weeks or

so--the post BMT discharge
period--was a sublime time for
us.

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.

On Monday, March 1, 1999 we

went to clinic and waited for the
lab results.
The results came back as we

 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
Male

age

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

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