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
