Acute leukemia is a neoplastic disorder characterized by uncontrolled proliferation of immature white blood cells in the bone marrow. It is classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). ALL is more common in children while AML is more common in older adults. Treatment for acute leukemia involves induction chemotherapy to achieve remission, central nervous system directed therapy to prevent relapse, intensification chemotherapy to further reduce disease burden, and continuation therapy to complete at least 2 years of treatment. Prognostic factors like age, white blood cell count, cytogenetics and early response to treatment determine risk-adapted therapy. Intensive multi-agent chemotherapy has improved survival rates to over 80% for

1. Acute leukemia
Dr Arun Sankar S
Moderator: Dr S Ghoshal
31/03/2006

2. Introduction
• Leukemia is a neoplastic disorder of the hematopoetic
system, charecterised by aberrant or arrested
differentiation.
• Uncontrolled clonal proliferation and accumulation of
blasts cells in the bone marrow and body tissues.
• Acute leukemia
• Sudden onset
• Aggressive disease
• Poorly differentiated cells with many blasts
• If left untreated is fatal within a few weeks or months

3. Introduction
• Classification
– Acute lymphoblastic leukemia ( ALL)
– Acute myeloid leukemia ( AML)

4. ALL
• MC cancer in children
– 25% of childhood cancers
– 30-40 per million.
– 3950 new cases annually in US
– >2500 in children & adolescents
– Incidence gradually increasing.
• Peak age gp – 2-3 years.
– Median age – 10 yrs
– Males – 1.3 times
– Whites – more common

5. AML
• Disease of advancing age
– Median age 65 yrs
• 90% of all acute leukemias
– 25% of all leukemias

6. Etiology – acute leukemia
• Genetic – 10-15% esp ALL
– Syndromes of impaired DNA repair
• Fanconi’s anemia
• Ataxia telengectasia
• Bloom’s syndrome
– Li Fraumeni syndrome (germline p53 mutation)
– Inherited immunodeficiency – Wiskott-Akdrich syndrome
– Neurofibromatosis type I
– Down syndrome
• < 3 yrs – megakaryoblastic AML
• Older children – ALL
– Primary mediastinal germ cell tumors - megakaryoblastic AML

7. Etiology – acute leukemia
• Occupational & environmental
– Chemicals
• Benzene
• Hydrocarbons, herbicides & thorotrast
– Cigarette smoking - AML
– Radiation
• Atomic bomb
• Radiation plant employees

8. Etiology – acute leukemia
• Secondary leukemias
– Chemotherapy
• Nitrosoureas, alkylating agents, procarbazine, podophyllotoxins
• Risk between 2-9 yrs
• 90% AML, very difficult to treat
– Radiotherapy
• Treated for benign disorders
• Malignancy
• Infections
– EBV
– ? HTLV-1

9. A L L

10. Classification - ALL
• Morphologic classification by FAB cooperative working
group
• L1
– Most common form in children (85%)
– Good prognosis
• L2
– Most common form in adults
– Same genetic abnormalities as L1
• L3
– Rarest form
– Identical to Burkitt’s lymphoma cells
– Mature B cell immunophenotype

11. L1 L2 L3
•Small cell
•Clumped
homogenous
chromatin
•Indistinct nucleoli
• Regular nucleus
•Scant cytoplasm-
slight basophilia
•Larger cells
•Heterogenous nuclear
chromatin
•Prominent nucleoli
•Irregular, indented
nucleus
•Moderate cytoplasm,
variable basophilia
• Large cell
• Fine homogenous
chromatin
• Prominent nucleoli
• Regular nucleus,
oval or round
• Moderate cytoplasm,
deep basophilia

12. • FAB classification – advantages
– Prognostic value . L1 better than L2. L3 has worst prognosis.
• criticism
– Does not correlate with immunophenotypic & cytogenetic
information.
– Subjective nature of classification
• Hence newer – immunophenotypic classification
– B cell
– T cell

13. • B cell ALL
– Express CD79a, CD19, HLA DR, CD10 antigen (cALLa) etc.
– 80-85% of childhood ALL
– 80% cALLa +, if negative – bad prognosis
• In infants, cALLa neg is assoc with 11q23 abnormalities & poor outcome.
– 3 types
– Some classifications – pro B cell group / transitional pre B group
Early pre B Pre B B cell
No surface or
cytoplasmic Ig
75% cases
Best prognosis
Cytoplasmic Ig
20-25%
Surface Ig
2%
L3 type

14. • T cell ALL
– Express CD3, CD7, CD2 or CD5
– Usually in a male, older age, with leukocytosis and mediastinal
mass.
– Prognosis bad, however with intensive therapy, has similar
outcome.

15. Clinical features
May present as
• Recurrent or severe infection.
• Pallor
• Bruising or petechiae
• Bone pain & limping gait.
• Lymphadenopathy – 50%
• Hepatosplenomegaly – 30-50%
• Extra medullary manifestations

16. – CNS
• 5% clinical symptoms
• Diffuse or focal neurological signs
• Raised ICP
• Seizures & nuchal rigidity
• Cranial N palsy – facial N
• Hypothalamic involvement
• Epidural infiltrate compressing the cord etc…
– Anterior mediastinal mass
• 10% cases
• Infiltration of thymus
• Usually T cell type
• Life threatening tracheobronchial / cardio vascular
compression – prompt chemo or XRT.

17. – Genito-urinary
• Clinical testicular involvement – rare
• Occult involvement – 21%, not clinically significant.
• Ovarian involvement – 30%
• Renal enlargement – leukemic infiltration/ hyperuricemia or
pyelonephritis.
– Bone and joint manifestations
• In 40 % - limp or painful bones
• Bone pain due to – direct leukemic infiltration of
periosteum, periosteal elevation, bone infarction, or
expansion of marrow cavity.
– Ocular manifestations
• In 33%
• Retinal haemorrhages – MC
• Ocular motor palsies & papilledema, indicate meningeal
leukemia – prompt XRT needed, if optic N involved.

18. Prognostic factors
• Age
• Strong prognostic factor
• Infants – high risk of Rx failure
– MLL gene rearrangement 11q23 common
– Associated with – high initial TC, CNS leukemia, cALLa –ve
• 1-9 years – best prognosis
• Adolescents better prognosis if Txed on pediatric & not adult
ALL protocols.
• WBC count at diagnosis
– > 50,000/μl – increased risk of treatment failure

19. • CNS status at diagnosis
– CNS 1 – CSF < 5 cells/μl & cytospin negative for blasts
– CNS 2 – CSF < 5 cells/μl & cytospin positive for blasts
– CNS 3 – CSF ≥ 5 cells/μl & cytospin positive for blasts
• ALL with CNS 2&3 are at higher risk for Tx failure both
within CNS & systemically
• Gender
– Girls, slightly better
– Boys, at increased risk of testicular, BM & CNS relapse.
• Morphology
– L1 – early pre B – good prognosis
– T cell - bad

20. • Cytogenetics
– Chromosome number
• Hyperdiploidy (> 50 chr or DNA index – 1.6) – good
– Seen in 25% B cell ALL, rare in T cell
• Trisomies 4, 10, 17 – good
• Hypodiploidy – treatment failure.
– Chromosome translocation
• TEL-AML1 t(12;21) in 25% B precursors – excellent
• Philadelphia chr t(9;22) – older pts with B precursors –
unfavourable
• MLL (11q23) gene involvement, usually infants - poor

21. • Early response to treatment
– Day 7 or 14 BM response
– Day 7 peripheral blood response
– Minimal residual disease by PCR at end of induction phase.

22. Investigative workup
• Establishing diagnosis
– Peripheral blood film, counts
– Bone marrow examination.
– Cytogenetic studies & immunophenotyping – if possible.
• Radiology
– CXR – LN, mediastinal widening, infections.
– USG Abd – renal size, hepatospenomegaly.
– Skeletal X-ray if symptoms.
• Biochemical
– RFT, electrolytes, uric acid, phosphate & Calcium.
– LFT.
• Microbiology
– Culture & sensitivity.

23. Treatment of ALL
• Over last 5 decades, dramatic improvement in the
prognosis.
• Single agents in 1950’s
• Combination agents in 1960’s
– Leukemia in CNS as initial site of relapse became
progressively more evident.
– Concept of pharmacological sanctuary - CNS
• Leukemic cells, even if subclinical, were present in CNS of all patients.
Protected from systemic chemotherapy by BBB.
• Radiation to CNS in 1970’s
– Pivotal step boosting long term DFS to > 50%
• Intensive therapy since 1980’s with good supportive care
– Complete remission > 95%
– Long term EFS > 80%

24. Phases of treatment
• 4 phases
• Remission induction
• CNS – directed therapy
• Intensification or consolidation
• Continuation

25. Remission induction
• aim
– Induce complete remission. – rapidly reduce leukemic cell
burden to a clinically & hematologically undetectable level.
• hematologic remission
– Normocellular BM with ≤ 5% blasts
– No blasts in peripheral blood
– Granulocyte count > 1000
– Platelet count > 1 lakh.
• complete remission
– Above criteria +
– Absence of any signs & symptoms of extramedullary disease.
• Duration of most regimes – 4-6 wks.

26. Remission induction
• Drugs
– Atleast 3 agents
• L-asparaginase 6000 u/m2 IM
• Vincristine 1.5 mg/m2 IV
• Prednisolone 40mg/m2 PO
• Daunorubicin 30 mg/m2 IV
4 drug Rx – better survival in high risk pts. ? Benefit for low risk
However, high short term morbidity esp.- neutropenia, infections.
– Initiation of CNS therapy – integral component.
• IT methotrexate <2 yrs – 8mg, 2-3yrs – 10mg, >3yrs – 12mg
±
• IT cytarabine <2 yrs – 30mg, 2-3yrs – 50mg, >3yrs – 70mg

27. Remission induction
Methotrexate IT
L-asparaginase
Vincristine
Prednisolone
PGI ALL
0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
1
4
1
5
1
6
1
7
1
8
1
9
2
0
2
1
2
2
2
3
2
4
2
5
2
6
2
7
2
8
2
9
Cytarabine IT
Methotrexate IT
L-asparaginase
Vincristine
Prednisolone
MRC ALL 97/01 0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
1
4
1
5
1
6
1
7
1
8
1
9
2
0
2
1
2
2
2
3
2
4
2
5
2
6
2
7
2
8
2
9

28. Remission induction
0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
1
4
1
5
1
6
1
7
1
8
1
9
2
0
2
1
2
2
2
3
2
4
2
5
2
6
2
7
2
8
2
9
MCP841 – TATA, AIIMS, Adayar

29. Remission induction
• Failure to achieve remission
– Less than 5%
– Use 2nd line agents – cytarabine, teniposide, daunomycin,
idarubicin.
– Ideally, after remission they should be considered for allogenic
stem cell transplantation

30. CNS treatment
• Initiated during induction therapy
• Definitive CNS Rx started immediately after induction.
– May be delayed by several months, if initial CSF is negative.
• Radiation therapy
– First modality, successfully used.
– 2400 – 1200 cGy to whole brain.
– Should be given to all patients with blasts in CSF.
• Intrathecal therapy
– IT MTx – induction and consolidation phases, along with radiation.
– IT MTx – induction, consolidation & continuation phases with intensive
systemic therapy, avoiding radiation in patients with low risk. (CCG study)

31. Intensification / consolidation
• Goal
– To further reduce the disease burden. (1010 blasts-at end of remission)
– Early studies – if no further Rx, most patients relapse with a median of
2-3 months.
– Designed to minimise the development of drug cross resistance.
– On some protocols, intensification delivered immediately after
remission – early intensification
Others – after a period of less intensive therapy – late intensification.
– Both low risk & the high risk groups benefit from these intensive cycle
of chemotherapy
– Anthracycline – doxo/dauno or high dose MTx
L- asparaginase, vincristine, steroids, cytarabine, endoxan
6 TG or 6 MP. Or various combinations of these.
– Various regimes exist, optimal treatment unknown.

32. Intensification / consolidation
• Examples
– PGI
• Early intensification (week 5-6)
– continue PDN for 1wk, taper off by day 44
– Vincristine – day 29, 63.
– Daunorubicin – 45mg/m2 IV day 29, 31
– Etoposide 100mg/m2 IV alternate day x 5 (29,31,33,35,37)
– Cytarabine 100mg/m2/dose BD IV –alternate day x 5
– 6TG – 60mg/m2 PO alternate day x 5
• CNS therapy (week 9-11), continuation phase (week 11-20)
• Late intensification ( week20-21) – instead of PDN – dexona
6mg/m2
• UK ALL group – both early & delayed intensification has
superior outcome than just one.
also three cycles better than two. –Eg- UK MRC ALL 97/01.

33. MCP841

34. Continuation
• Less intensive therapy to complete at least 2 years.
• Weekly low dose MTx
daily oral 6 MP
± pulses of steroids + vincristine ( ? Benefit)
• How long ?
– Study by CCG – no significant benefit 5 yrs vs. 3 yrs.
– Study by UK ALL group – 2 yrs vs. 3 yrs – no significant survival
advantage.
– Boys however benefit from a more prolonged treatment.
– ? Even shorter duration with more intensive regime
• BFM group – 18 vs. 24 months – higher relapse
• Tokyo children’s cancer study group – only 12 mnth. – high relapse.
– Standard
• 2 years – female
• 3 years – male

35. Special subsets
• Philadelphia chromosome positive ALL
– t(9;22)(q34;q11)
– 5% of children, 20% adult ALL
– Dismal prognosis (EFS 0-25%)
– Allogenic stem cell transplantation may improve survival.
• Infants
– Poor prognosis & increased vulnerability to toxic effects of Rx.
– Biologically distinct form – MLL gene rearrangement.
– Very high dose cytarabine – may have a benefit.
– DFCI ALL protocol – early intensification with high dose cytarabine,
MTx and delayed cranial irradiation.
– EFS <40%.

36. Risk adapted therapy
• Goal
– “Treat away” adverse presenting features, so that cure rates are
similar to low risk disease
– Reduction in the use of elements with significant toxicity in low risk
disease.
High risk
• BCR/ABL +
• hypodiploidy (<44 chr)
• MLL gene rearrangement
Standard risk Intermediate risk
• Age >1 & < 10 yrs
• TLC < 50,000
• age > 10 yrs
• TLC > 50,000
• > 25% blasts on day 15 or
> 5% blasts on day 29 in BM
while on Rx.

39. Vincristine D1,8,15,22 & 29
Pred + Mtx + VCR + 6 MP
Dexa + VCR + Doxo + L Aspar +
Cyclo + TG + Ara-C
Pred + Mtx + VCR +
6 MP
Pred + Mtx + VCR + PEG L Aspar
Regimen A
Pred + L Aspar
Regimen B
Pred+ L Aspar + Dano
Pred + VCR
+ 6 MP
Pred + Mtx + VCR + 6 MP
Dexa + VCR + Doxo + L Aspar
+ Cyclo + TG + Ara-C
“Augmented BFM”
Cyclo + Ara-C + 6 MP +
VCR + PEG L Aspar
Pred + Mtx + VCR + PEG L Aspar
Regimen C
Pred+ L Aspar + Dano
Cyclo + Ara C
+ 6 MP

40. Adult ALL
• Poorer prognosis
• Increasing incidence of Philadelphia chr.(20%)
– Those who have CR – considered for allogenic BMT.
• Older age –itself poor prognosis.
• Poorer tolerance to intensive chemotherapy.
• 35-40% 2 year survival with aggressive treatment & best
supportive care.
• Young adults better treated with pediatric protocols.

41. Adult ALL
• PGI protocol (modified BFM)
• Induction
– Phase A (1-4 wks)
• PDN -60mg/m2 PO
• Vincristine -1.5 mg/m2 IV weekly
• Daunorubicin -30 mg/m2 IV weekly
• L-asparaginase -70,000 units/m2 IV twice weekly (2nd wk onwards)
• Endoxan -800mg/m2 IV day 1, 28
• BM examin for remission
– Phase B (5-9 wks)
• Endoxan IV wk 5, 7
• Cytarabine 75 mg/m2 -4 days/wk wk 5,6,7,8
• IT MTx – 12mg/m2 upto 15 – wkly
• XRT week 7 onwards.

42. • Consolidation (wk 10-14)
– Cytarabine 100mg/m2 x 4 days , wk 10 & 13
– Etoposide – same dosage
– IT MTx – week 12
– BM examination.
• Reinduction
– Phase 1 (wk 15-18)
• Prednisolone
• Vincristine
• Doxorubicin
• L-asparaginase
– Phase 2 (wk19-22)
• Endoxan
• Cytarabine
• IT MTx
– BM examination

43. • Maintanence phase
• T. 6 MP 75 mg/m2 daily
• T. MTx 25mg/m2 weekly
• Vincristine 1.5 mg/m2 monthly IV
• PDN 60 mg/m2 x 5days monthly
• IT MTx 3 monthly
– 2 years in females
– 3 years in males
• Relapse
• Ifosfamide 1.6- 4 gm/m2 D1-5
• Etoposide 100mg/m2 D1-5 max 2 cycles
• Maintain with D1-3 CCT for 1 year.

44. Cranial Irradiation.
• Indication
– Prophylactic
– Therapeutic
Prophylactic
• Early evidence
– Studies V & VI from SJCRH ( 1962-67)
• CSI to 24 Gy/16# - isolated CNS relapse 64% to 4%.
• 12 Gy not found useful.
• However, acute myelosuppression, late musculoskeletal
dysplasia.
– Study VI
• CSI vs. cranial XRT + IT MTx.
• Equivalent with 8 % risk of relapse.
– Study VII
• IV MTx & XRT in close proximity avoided.
• Oral MTx & 6 MP as maintenance decreased relapse.

45. – CCSG study 101
• 24 Gy CSI+ liver, spleen, gonads
• 24 Gy CSI
• 24 Gy cranial + IT MTx
• IT MTx
– Radiation definitely superior over IT MTx alone.
– Cranial RT + IT MTx superior to CSI
– CALGB studies
• In low risk ALL, CNS relapse rate is 5% regardless of CNS Rx.
• Recent trends
– In US, avoid XRT in all but high risk patients, avoiding long term
effects.

46. – CSSG trial – for low risk.
• Similar results if XRT substituted with IT MTx throughout
induction, consolidation & maintenance.
– CSSG 105 – intermediate risk.
• IT MTx with intensive CCT equivalent to
standard CCT with XRT.
• IT MTx alone with standard CCT – high CNS recurrence(20%).
– ALL high risk patients require XRT
• T cell ALL
• Counts > 1 lakh
Therapeutic
– All patients with CSF blasts + ( at diagnosis or relapse)
• Some exclude CSF -2 ( give more intense IT CCT), if TLC is normal.

47. • PGI
– All children were treated with XRT
• No strict risk stratification had been done.(? Are risk
factors same in indians)
• All children treated as high risk.
• Repeated lumbar puncture avoided. (infection )
• Bloody puncture at any time- relapse.
• New protocol (UK MRC ALL 97/01)
– Risk stratification, & no XRT for low risk patients.
– All adults with ALL

48. • Technique
– Volume: include all cranial meninges, including those
surrounding the optic nerve in the retro-orbit. And
extending down the spinal cord to level of L2.
– To keep lens dose to minimum.
– Immobilisation - supine position.
– Lateral opposed fields.
1. Rectangular field, with one edge running parellel to
Reid’s baseline
2. Using asymmetrical jaws & custom blocks, and keeping
the isocentre 15 mm behind the cornea, helps reduce
lens dose.

49. • Dose.
– Therapeutic – 2400 cGy /16#
– Prophylactic – 1800 cGy/12#
- 1200 cGy/8# with intensive CCT. (BFM-90 protocol)
– hyperfractionation ?
• The Dana Farber ALL consortium
• No definite advantage in relapse rates.
• Need for anesthesia twice daily.

50. Other roles of radiotherapy
• Testicular disease
– At presentation.
– At relapse.
Volume: both sides testis & spermatic cord upto the deep inguinal ring.
Positioning: supine
lead shield under scrotum to save perineum
penis taped against abdomen.
Field : direct anterior
Dose: 2400cGy/12#

51. Other roles of radiotherapy
• Retinal / optic nerve involvement.
– May present with mono-ocular blindness.
– Prompt Radiotherapy needed to salvage vision.
– Unilateral field or parallel opposed field
– 3x4 cm field, starting at the orbital rim
– If U/L – depth of 3 cm
– Dose: 2500 cGy/12#
• Severe bone pain.
– 1000 – 1500 cGy in 2-3 #

52. Other roles of radiotherapy
• Anterior mediastinal mass with severe dyspnoea
• Facial N palsy
• Treat from base of brain to peripheral extension over the
cheek.
• 2500 cGy
• Treat within 24 hrs – prompt restoration of motor power.

53. Follow up
• Monthly blood counts & clinical examination -2 years.
– Then at decreasing frequency.
• Most important clinical assessment: testis
• Routine bone marrow not indicated.

54. Relapse
Despite all this.
20-30 % relapse.
If EFS < 1 year, very bad prognosis.
• Bone marrow relapse
– Symptoms similar to initial presentation or on routine blood film.
– Confirm by bone marrow examination.
– Induction of remission – same regimen. 70-90% (Bcell)
– Maintaining remission
• Prolonged intensive CCT with CNS therapy.
Or
• High dose chemoradiotherapy & autologous/allogenic BMT.

55. • Standard CCT – 18% survival
• Intensive CCT – 30-40% ( very intensive-65%)
• Allogenic BMT – 25-60% (mortality 15-30%)
• Unrelated donor – 20-30%
• Autologous – 40-50% in good risk pts.
• Isolated CNS relapse -10%
– Headache, vomiting, raised ICP, FND, convulsions.
– CSF study. Look for relapse elsewhere – BM.
– 90% response with CNS directed therapy.
• IT MTx prolonged, with cranial XRT.
– They relapse later on in the BM.. Hence systemic CCT must.

56. • Isolated testicular relapse.
– Painless swelling of testicles.
– Biopsy B/L testis. Look for disease elsewhere.
– Systemic chemotherapy + testicular irradiation. ± CNS therapy.
• Relapses in other extra medullary sites
– Usually managed by local XRT & systemic therapy.

57. Complications of treatment
• Acute
– Metabolic
• Tumor lysis syndrome
– Anemia, thrombocytopenia
– Caogulation abnormality – T cell ALL, asparaginase –thrombosis
– Infection – bacterila, fungal & PCP
– Typhlitis
– Acute neurological toxicity – seizures, somnolence syndrome
– Pancreatitis
• Late effects
– CNS – low IQ, leukoencephalopathy
– Growth
– Bony morbidity- osteopenia, # , osteonecrosis
– Second malignancies – gliomas, AML

58. Summary
presentation
Investigative workup
& stabilisation
CSF study + day 1 IT
MTx
Induction + IT MTx
Bone marrow
Early intensification
CNS therapy (RT+ IT
MTX
continuation
Late intensification
continuation
2nd line agents –
BMT ideally
Follow up
BM relapse CNS relapse testicular

59. A M L

60. AML
• Disease of the elderly.
• Gradual improvement in survival, still majority patients
die from their disease.
• In older age group, the outcome remains frustratingly
disappointing.

61. Classification - FAB
• M0 - Minimally differentiated AML
– 5% cases.
– blasts are negative for B and T lymphoid antigens
– Negative or < 3% blasts stain for MPO, Sudan black and NSE
– Myeloid antigens : CD13, CD33 and CD11b are positive.
– Need to distinguish from ALL

62. • M1 Myeloblastic without maturation
– 10% cases.
– >90% myeloblasts.
– MPO & Sudan black >3%
– CD13,33,117
– Need to distinguish from ALL.
– Worse prognosis.

63. • M2 AML with maturation.
– 30-45% cases.
– > 20 % myeloblasts.
– Auer rods +
– MPO, lysozyme +
– t(8:21) abnormality- favourable prognosis
– Granulocytic sarcomas – chloromas - common

64. • M3 - Acute Promyelocytic Leukemia (APML)
– 8%
– Auer rods/ faggot cells++
– MPO +++
– Hypergranular & microgranular
– Assoc with DIC, bleeding
– t(15:17) is diagnostic
– Sensitive to ATRA.

65. • M4 Acute Myelomonocytic Leukemia
– 15-25% cases
– Increased CNS involvement.
– Monocytes & promonocytes 20-80%
– M4 with eosinophilia ((M4-Eo),
assoc with del/inv 16q
• M5a Acute Monoblastic Leukemia 8%
• M5b AMoL with differentiation 5%
• > 80 % monocytic lineage cells.
• More organomegaly, tissue infiltration
• Rectum, skin nodules, gum
• t(9;11) & t(11q;23)

66. • M6 – acute erythroid leukemia (DiGuglielmo’s disease)
– 5-6%
– >50% erythroid precursors in the entire nucleated cells of BM
– > 20% myeloblasts
– DD – megaloblastic anemia.

67. • M7 acute megakaryoblastic leukemia
– 3-5%
– >50% blasts of megakaryocytic lineage.
– Platelet peroxidase +
– MPO & Sudan black -ve
– Lytic bone lesions in children.
– Mediastinal germ cell tumors in male.

68. WHO classification
1. AML with recurrent cytogenetic translocation
• t(8;21)
• APML t(15;17)
• inv16
• 11q23 abnormality
2. AML with multilineage dysplasia
• With prior MDS
• Without prior MDS
3. AML, therapy related
• Alkylating agent related
• Epipodophyllotoxin related
• Other types
4. AML not otherwise categorized
Same as FAB classification.

69. Symptoms & signs
– Weakness – leading symptom
– Fever & bleeding manifestation more common than in
ALL
– LADenopathy, HSM, less common
– CNS involvement – rare.
– Gingival hypertrophy, skin nodules & pinkish patches –
M4&5

70. Prognostic factors
– Older age group – poor
– Cytogenetics
– Prior dysplasia / secondary AML
– High presenting TLC
– KPS
– Male sex.
Cytogenetic classification
Favourable intermediate unfavourable
t(15;17) +8, -Y, +6, del(12p) del 5q, del 7q
inv 16 normal t(8;21) with del 9q
t(8;21) without del 9q 21q, del 9q, t(6;9)
t(9;22)
complex karyotype

71. Treatment
• 3 phases
– Remission induction
– Post remission treatment.
– maintenance

72. Non M3 - treatment
• Remission induction.
– Aim: cytoreduction to achieve CR
– CALGB trial 2 decades ago
• 3+7 induction regime.
• Daunorubicin 45mg/m2 D1-3 IV
Cytosine 100 mg/m2 BD D1-7 IV
• Marrow on day 14 ---60-75% CR
Other regimes
– Idarubicin vs. daunorubicin
– Mitoxantrone vs. daunorubicin
• Both found to have superior to daunorubicin.
• But with higher toxicity, and only in younger patients.
• Also unequal doses given.

73. – Higher dose cytarabine
• Higher response rate
• Too toxic
– Hence the standard for induction is the 3+7 regime.
• Consolidation
– 109 to 1010 cells still are circulating !!
– The options
• High dose chemotherapy
• Auto/ allo stem cell transplantation.
– High dose therapy
• Inj cytarabine 3gm/m2 BD D1, D3, D5.
• 3 consolidations.

74. • Stem cell transplantation
– Allogenic
• Limited to younger patients (<45 yrs)
• 50 – 55 % survive the procedure
• 15 % relapse
– Autologous
• Upto 60 years
• No GVleukemia effect.
• Leukemic cell reinfusion
– Comparing stem cell transplant with Chemotherapy.
• Significant impact in reducing relapse risk.
– In surviving patients !!
• No survival benefit.

75. • Maintanence ( optional)
– Tab 6 TG – 80mg BD D1-4
– Inj cytarabine 100mg/m2 SC on D5
– Continued for 6 months.

76. Older age group
• Unfavourable prognostic factors
• Inability to withstand intensive therapy.
• The decision to treat or not ?
• Lower doses of drugs.
• Inj cytosine 10mg/m2 SC 7-14 days
• Inj mitoxantrone 6mg/m2 IV D1-3
• T etoposide 100mg OD 7-14 days
• T 6 TG 40mg BD 7-14 days
– Assess monthly

77. M3 AML
• Induction
– ATRA + anthracycline ± cytarabine
• Cap ATRA 45 mg/m2 BD
• Daunorubicin – 50mg/m2 D1-3
• Consolidation
– Daunorubicin ± cytarabine
• Daunorubicin – 50mg/m2
• Cytarabine 100mg/m2 IV BD x 7 days ( if high risk)
• Maintenance
– ATRA ± low dose CCT
• ATRA 45 mg/m2/day BD x 15 days 3monthly
• T 6-MP 75 mg/m2 daily HS
• T MTx 20mg/m2 weekly.
Side effects of ATRA
Hyperleukocytosis
Retinoic acid syndrome

78. Newer approaches
• New chemotherapeutic drugs
• Clofarabine
• Arsenic trioxide
• Modulation of drug resistance -- PSC-833
• Sensitization
• Anti-angiogenesis
• Modulation of cell signaling
• Tipifarnib
• Immunotherapeutic
• Gemtuzumab Ozogamicin

79. SUPPORTIVE CARE
• Prevention & management of infections
– Antibiotics, antifungals
– Barrier nursing
• Support during bonemarrow aplasia period
– Blood products
– Management of DIC as in M3 AML
• Adequate hydration, allopurinol
• Management of metabolic complications

80. • Treat me to cure me ... I
want to have kids like me
to worry about...
• Ask me what is the
hardest part to me?
• Ask me what you can do
to help? But ask me in a
way I can understand...
• Treat me like you would
have wanted to be
treated way back when...
Cancer Treatment
… from the eyes of a child

81. Thank you for
wanting to
learn…and for
making a difference
in the lives of
children and young
adults
Photograph by K. Tartakoff