Acute

esLeukemia
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-Harrison’s 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: Down’s Syndrome, Bloom’s,
Fanconi’s 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 D’s 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 D‘s
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 D’s 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