1. Acute Leukemia
Rakesh Biswas
MD, Professor, Department of Medicine,
People's College of Medical Sciences,
Bhanpur, Bhopal, India

2. A 16 year old girlA 16 year old girl
Extreme pallorExtreme pallor
gum bleeds, Purpura,Withgum bleeds, Purpura,With
Lymphadenopathy andLymphadenopathy and
HepatosplenomegalyHepatosplenomegaly

3. Possible causes:Possible causes:
Investigations and treatmentInvestigations and treatment

4. Only a week later, D was illOnly a week later, D was ill
again, with a fever, severeagain, with a fever, severe
headache, and extremeheadache, and extreme
lethargy.lethargy.

5. During a sunny spring weekend,During a sunny spring weekend,
D would go outside to play, onlyD would go outside to play, only
to return minutes laterto return minutes later
exhausted, flopping herself ontoexhausted, flopping herself onto
the sofa to restthe sofa to rest

6. LeukemiaLeukemia
Group of malignant disorders of theGroup of malignant disorders of the
hematopoietic tissues characteristicallyhematopoietic tissues characteristically
associated with increased numbers ofassociated with increased numbers of
white cells in the bone marrow and / orwhite cells in the bone marrow and / or
peripheral bloodperipheral blood

7. Once inside the van and on ourOnce inside the van and on our
way out of the clinic parking lot,way out of the clinic parking lot,
she asked,she asked,
"Dad, what is leukemia?""Dad, what is leukemia?"
"Can I die from this?""Can I die from this?"

8. Classification
 Classified based on cell type involvedClassified based on cell type involved
and the clinical courseand the clinical course
 1.1. AcuteAcute ::
 ALLALL
 AMLAML
2.2. ChronicChronic ::
 CLLCLL
 CMLCML

9. Subclassification
ALLALL
Common type( pre-B)Common type( pre-B)
B-cellB-cell
T-cellT-cell
UndifferentiatedUndifferentiated

10. 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.

13. Myelomono

14. AMLAML
French-American-British (FAB) ClassificationFrench-American-British (FAB) Classification
M0: Minimally differentiated leukemiaM0: Minimally differentiated leukemia
M1: Myeloblastic leukemia without maturationM1: Myeloblastic leukemia without maturation
M2: Myeloblastic leukemia with maturationM2: Myeloblastic leukemia with maturation
M3M3: Hypergranular promyelocytic leukemia: Hypergranular promyelocytic leukemia
M4Eo: Variant: Increase in abnormal marrowM4Eo: Variant: Increase in abnormal marrow
eosinophilseosinophils
M4:M4: Myelomonocytic leukemiaMyelomonocytic leukemia
M5M5: Monocytic leukemia: Monocytic leukemia
M6: Erythroleukemia (DiGuglielmo's disease)M6: Erythroleukemia (DiGuglielmo's disease)
M7: Megakaryoblastic leukemiaM7: Megakaryoblastic leukemia
Ref-Harrison’s Principle of Internal Medicine

15. CLLCLL
B-cell: commonB-cell: common
T-cell: rareT-cell: rare

16.  CMLCML
Ph +vePh +ve
Ph –ve, BCR-abl +vePh –ve, BCR-abl +ve
Ph –ve, BCR-abl -vePh –ve, BCR-abl -ve
Eosinophilic LeukemiaEosinophilic Leukemia
 Ph: Philadelphia chromosomePh: Philadelphia chromosome
 BCR: Breakpoint cluster region; abl : Abelson oncogeneBCR: Breakpoint cluster region; abl : Abelson oncogene

17. Acute Myeloid Leukemia
( AML)
 Malignant transformation of aMalignant transformation of a
myeloid precursor cell ;myeloid precursor cell ;
usually occurs at a very early stageusually occurs at a very early stage
of myeloid developmentof myeloid development
 Rare in childhood & incidenceRare in childhood & incidence
increases with ageincreases with age

18. Etiology
Unknown / De-novo !! In majorityUnknown / De-novo !! In majority
Predisposing factorsPredisposing factors::
 Ionizing radiation exposureIonizing radiation exposure
 Previous chemotherapy : alkylating agentsPrevious chemotherapy : alkylating agents
 Occupational chemical exposure : benzeneOccupational chemical exposure : benzene
 Genetic factors: Down’s Syndrome, Bloom’s,Genetic factors: Down’s Syndrome, Bloom’s,
Fanconi’s AnemiaFanconi’s Anemia
 Viral infection ( HTLV-1)Viral infection ( HTLV-1)
 Immunological : hypogammaglobulinemiaImmunological : hypogammaglobulinemia
 Acquired hematological condition -SecondaryAcquired hematological condition -Secondary

19. Epidemiology
 M > FM > F
 ALL which predominantly affectsALL which predominantly affects
younger individualsyounger individuals
 AML – adults and the elderlyAML – adults and the elderly
 Median age gp-65yrsMedian age gp-65yrs
 Geographical variation-noneGeographical variation-none

20. Clinical features
GeneralGeneral ::
Onset is abrupt & stormyOnset is abrupt & stormy
(usually present within 3 months)(usually present within 3 months)
Bone marrow failureBone marrow failure
(anemia, infection ,bleeding)(anemia, infection ,bleeding)
Bone pain & tendernessBone pain & tenderness

21. Specific:Specific:
 M2M2 : Chloroma:-presents as a mass lesion: Chloroma:-presents as a mass lesion
‘tumor of leukemic cells’‘tumor of leukemic cells’
 M3M3 : DIC: DIC
 M4/M5M4/M5 : Infiltration of soft tissues,: Infiltration of soft tissues,
gum infiltrationgum infiltration, skin, skin
deposits ,Meningeal involvement-headache,deposits ,Meningeal involvement-headache,
vomiting, eye symptomsvomiting, eye symptoms

23. Skin Infiltration with AML (Leukemia Cutis)

24. Diagnosis
 Blood countBlood count ::
WBC usually elevated (50,000-WBC usually elevated (50,000-
1,00,000 / cmm ); may be normal or1,00,000 / cmm ); may be normal or
low; oftenlow; often
anemia & thrombocytopeniaanemia & thrombocytopenia
 Blood filmBlood film : (as above): (as above)
Blast cellsBlast cells

25. P. Smear AML

26.  Bone marrow aspirate & trephineBone marrow aspirate & trephine::
Hypercellular,Hypercellular,
blast cellsblast cells ( > 20%),( > 20%),
presence ofpresence of Auer rods -Auer rods - AML typeAML type
 CytochemistryCytochemistry ::
Special stains toSpecial stains to
differentiate AML from ALL ;differentiate AML from ALL ;
PositivityPositivity with Sudan black &with Sudan black &
Myeloperoxidase (MPO) in AMLMyeloperoxidase (MPO) in AML

27. Jemshidi trephine &
Salah aspiration needle

28. Auer Rods in Leukemia cells

29. MPO (right) & Sudan black (left)
showing intense localised positivity
in blasts

30.  Confirmation:Confirmation:
ImmunophenotypingImmunophenotyping
Molecular geneticsMolecular genetics
Cytogenetics: ChromosomalCytogenetics: Chromosomal
abnormalitiesabnormalities

31. Other InvOther Inv::
 Coagulation screen,Coagulation screen,
fibrinogen,fibrinogen,
D- dimerD- dimer
 RFT, LFTRFT, LFT
 LDH, Uric acidLDH, Uric acid
 UrineUrine
 CXRCXR
 ECG, ECHOECG, ECHO

32. Management
I.I. Supportive careSupportive care ::
 Anemia – red cell transfusionAnemia – red cell transfusion
 Thrombocytopenia – plateletThrombocytopenia – platelet
concentratesconcentrates
 Infection – broad spectrum IV antibioticsInfection – broad spectrum IV antibiotics
 Hematopoietic growth factors :Hematopoietic growth factors :
GM-CSF, G-CSFGM-CSF, G-CSF
 Barrier nursingBarrier nursing
 Indwelling central venous catheterIndwelling central venous catheter

34. Metabolic problemsMetabolic problems ::
Monitoring hepatic /Monitoring hepatic /
renal / hematologic function;renal / hematologic function;
Fluid &Fluid &
electrolyte balance, nutritionelectrolyte balance, nutrition
Hyperuricemia- hydration, AllopurinolHyperuricemia- hydration, Allopurinol
Psychological supportPsychological support

35. The white blood cell count in her
peripheral blood was about
550,000.
Her bone marrow was packed
with leukemia blasts."

36. 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.

37. 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.

38. SPECIFIC THERAPHY:SPECIFIC THERAPHY:
ChemotherapyChemotherapy ::
InductionInduction: (4-6 wks): (4-6 wks)
vincristine, prednisone,vincristine, prednisone,
anthracycline,anthracycline, (idarubicin or(idarubicin or
daunorubicin)daunorubicin)
cyclophosphamide, and L-asparaginasecyclophosphamide, and L-asparaginase

39. ConsolidationConsolidation:: (multiple cycles of(multiple cycles of
intensive chemotherapy given over a 6 to 9intensive chemotherapy given over a 6 to 9
month period).month period).
Cytosine arabinoside, high-doseCytosine arabinoside, high-dose
methotrexate, etoposidemethotrexate, etoposide
anthracycline,anthracycline, (idarubicin or daunorubicin)(idarubicin or daunorubicin)

40. Maintenance phase:
(18 to 24 months).
LPs with intrathecal MTX every 3
months,
Monthly vincristine,
Daily 6-MP, and weekly MTX.

41. At day 29 of the inductionAt day 29 of the induction
protocol D was declared to be inprotocol D was declared to be in
complete remission.complete remission.
We were all relieved with thisWe were all relieved with this
news.news.

42. Step two was the next phase ofStep two was the next phase of
treatment called consolidationtreatment called consolidation
therapy.therapy.
This entailed multipleThis entailed multiple
combinations of drugscombinations of drugs
administered on a rotationaladministered on a rotational
basis (on various weeks) for thebasis (on various weeks) for the
next six months.next six months.

43. For instance, she would receiveFor instance, she would receive
an infusion of methotrexate for aan infusion of methotrexate for a
couple of days and then take 6-couple of days and then take 6-
MP by mouth for a week.MP by mouth for a week.
Another cycle included VM-26Another cycle included VM-26
(Teniposide) and Ara-C.(Teniposide) and Ara-C.

44.  Complete remissionComplete remission ( CR):( CR):
< 5% blast cells in normocellular bone< 5% blast cells in normocellular bone
marrowmarrow
 AutologousAutologous BMTBMT ::
Can be curative in younger patient (<Can be curative in younger patient (<
40-50 yrs)40-50 yrs)

45. Exactly 5 months since herExactly 5 months since her
diagnosis, and 16 weeks ofdiagnosis, and 16 weeks of
remission…remission…
"We're at the clinic. D has"We're at the clinic. D has
relapsed. Her white count isrelapsed. Her white count is
27,000."27,000."

46. The Consolidation protocol hadThe Consolidation protocol had
been dropped and replaced withbeen dropped and replaced with
a new induction protocol.a new induction protocol.
After the bone marrow aspiration toAfter the bone marrow aspiration to
determine the extent of the leukemiadetermine the extent of the leukemia
relapse, she was given doxirubicin,relapse, she was given doxirubicin,
vincristine and L-asparaginase.vincristine and L-asparaginase.

47. For several days following D‘sFor several days following D‘s
discharge from the bonedischarge from the bone
marrow transplant unit, all of usmarrow transplant unit, all of us
loaf around the house andloaf around the house and
recuperate from our 90 dayrecuperate from our 90 day
marathon…marathon…

48. ……the first 30 days representingthe first 30 days representing
Ds' relapse and the inductionDs' relapse and the induction
therapy to obtain a secondtherapy to obtain a second
remissionremission

49. Back in fighting form, DBack in fighting form, D
proceeds directly to the final 30proceeds directly to the final 30
days of the marathon--thedays of the marathon--the
actual bone marrow transplant.actual bone marrow transplant.
BMT patients are in a delicateBMT patients are in a delicate
condition following dischargecondition following discharge

50. Looking back, the nine weeks orLooking back, the nine weeks or
so--the post BMT dischargeso--the post BMT discharge
period--was a sublime time forperiod--was a sublime time for
us.us.
D was home and was feelingD was home and was feeling
pretty good.pretty good.

51. As D’s hair began to growAs D’s hair began to grow
again, we rubbed her headagain, we rubbed her head
every night at the dinner table,every night at the dinner table,
wondering what color it waswondering what color it was
going to be or if it was going togoing to be or if it was going to
be curly or straight.be curly or straight.
We never found out.We never found out.

52. On Monday, March 1, 1999 weOn Monday, March 1, 1999 we
went to clinic and waited for thewent to clinic and waited for the
lab results.lab results.
The results came back as weThe results came back as we
feared.feared.
D had relapsed. Her whiteD had relapsed. Her white
count was 47,000. We werecount was 47,000. We were
devastated.devastated.

53.  III. PALLIATIVE THERAPHYIII. PALLIATIVE THERAPHY
Chemo, RT, Blood product supportChemo, RT, Blood product support

55. Prognosis
 Median survival without treatment is 5Median survival without treatment is 5
weeksweeks
 30% 5-yr survival in younger patients with30% 5-yr survival in younger patients with
chemotherapychemotherapy
 Disease which relapses during treatmentDisease which relapses during treatment
or soon after the end of treatment has aor soon after the end of treatment has a
poor prognosispoor prognosis

56. Poor prognostic factors
 Increasing ageIncreasing age
 Male sexMale sex
 High WBC count at diagnosisHigh WBC count at diagnosis
 CNS involvement at diagnosisCNS involvement at diagnosis
 Cytogenetic abnormalitiesCytogenetic abnormalities
 Antecedent hematologicalAntecedent hematological
abnormalities (eg. MDS)abnormalities (eg. MDS)
 No complete remissionNo complete remission

57. Two things that I will alwaysTwo things that I will always
remember about D: She was aremember about D: She was a
collector of many things, trinketcollector of many things, trinket
boxes, key rings.boxes, key rings.
But she was first and foremost aBut she was first and foremost a
collector of "FRIENDS."collector of "FRIENDS."

58. Among other things, she wrote:Among other things, she wrote:
"Hair loss is a side effect of"Hair loss is a side effect of
chemotherapy, and cancer is achemotherapy, and cancer is a
side effect of life."side effect of life."

59. Summary;
Learning Points

60. THANK YOUTHANK YOU