Acute myleoid leukemia basic

1. Acute Myeloid Leukemia

2. • Clonal expansion of myeloid blasts in blood, bone
marrow and other tissues.
• SEER = median age 68 yrs
• Exposure to petrochemicals, ionizing radiation,
benzene, pesticides
• < 5% cases are familial

3. Our data
• Median age= 29 years (27% pediatrics)
• M:F = 3:2
• C/F
1. Gum hypertrophy = 25%
2. Lymph node = 22%
3. Chloromas = 10%
4. Hepato-spleenomegaly = 30%
• High TLC = 31%

4. Work Up
• History/ Physical examination
• CBC LFT KFT + 2 D ECHO
• LDH, uric acid
• Peripheral smear
• Bone marrow core biopsy and aspirate
• Flowcytometry and Cytogenetic analysis
• Multiplex gene panel/comprehensive NGS
• PCR : NPM1, FLT3-ITD/TKD, CEBPA, BCR-ABL, PML-RARA, TP53, ASXL1,
RUNX1, KIT
• HLA typing
• CSF analysis
1. Symptomatic
2. High WBC > 40000
3. Monocytic differentiation
4. High Risk APL
5. Extramedullary disease
FLT3 +/-

6. Complex karyotype: 3 or more unrelated
chromosomal abnormalities in absence of WHO
designated translocation
Monosomal : presence of single monosomy
excluding X/Y chromosome with at least 1
additional monosomy or structural abnormality.

7. Good Intermediate Poor
CR 81% 50% 32%
3-DFS 46% 17% 2%
3-OS 45% 18% 4%

8. Our Data n= 407
Our data
Good risk 21%
Intermediate risk 69%
Poor risk 10%
T(8;21) 20%
Normal cytogenetics 60%
Complex 6%
monosomy 2%

9. • 70% achieved morphological CR, 8% require 2nd
induction, 8 % refractory AML
• Good risk = 84%
• Intermediate risk = 67%
• Poor risk = 54 %
Induction mortality was 18.7%
47% patients relapsed within 10 months
Median OS= 23.8 months

10. TRM score
• Age
• PS
• Secondary AML
• Albumin
• Creatinine
• WBC
• Peripheral blood blast percentage
• Race J Clin Oncol 29:4417-4423

11. TRM
• Physiologic age =60 years
CR rates= 60-85% vs 40 -60 %
More adverse cytogenetics, comorbidities
• NCI-CC vs non NCI ( 60 day mortality 12 vs 24%)

12. Treatment < 60 years
• 3+ 7 regime
• Daunorubicin 45-60 mg/m2 X 3 days + ARA-C 100
mg/m2 X 7 days
• Idarubicin 12 mg/m2 X 3days + ARA-C 100 mg/m2 X
7 days
• Daunorubicin 45-60 mg/m2 X 3 days + ARA-C 100
mg/m2 SC BD X 7 days

13. • Ida vs dauno = No OS
• Dauno 45 vs Dauno 90
CR rate (71 vs 57), OS = 24 vs 16 months
• Dauno 60 vs Dauno 90
CR rate (73 vs 75), 2 yr- OS = 59 vs 60 months
60 day mortality ( 5% vs 10%)
• More beneficial in young, low risk and intermediate
risk, FLT3-ITD.

14. Cytosar
• s/c vs IV
• 240 patients, non-inferior
• CR rate : 71 vs 70%
• 3 yr-OS = 60% vs 58%

15. Midostaurin
• oral multi-targeted TKI in patients with a FLT3
mutation
• 50 mg BD day 8-21 induction, maintenance
• RATIFY study:
• CR rates : 57 vs 54
• Median OS = 74.7 vs 24.6 mts.
• Nausea, febrile neutropenia, hypocalcemia,
transamnitis, mucositis, musculoskeletal pain
• Other drugs : Sorafenib, crenolanib, quizartinib

16. CD 33 AML
• Gemtuzumab Ozogamicin
• Antibody to CD33 combined with caleacheamicin.
• Dose = 3mg/m2 on day 1,4,7
• MRC-AML 15 trial = no benefit
• Meta-analysis :
• Favourable risk , 5 yr OS = 76 vs 55%
• intermediate risk , 5 yr OS = 34 vs 39%
• Thrombocytopenia, infections, electrolyte imbalance

17. CPX 351 /Vyseox
• a liposomal formulation of cytarabine and
daunorubicin ratio of 5:1.
• Secondary/ therapy related/ MDS related
• 3+7 vs CPX
• CR rate: 31 vs 57%
• OS = 5.9 vs 9.5 months
• Febrile neutropenia, Pneumonia, Hypoxia

18. Ventoclax
• oral inhibitor of the anti-apoptotic protein BCL-2
• Dose = 400 mg HMA, 600 mg LDAC
• Unfit for therapy
• Phase 1 b study, dose escalation study
• Age > 65 years, not fit for intensive chemotherapy
• WBC < 25000
• After 8.9 months, CR + CRi = 67%

19. Phase 3, randomized, double-blinded, multicenter,
Inclusion :
1. Pts with confirmed AML
2. Ineligible for intensive induction therapy due to medical
comorbidities and/or age > 75 years
Exclusion: prior HMA use
Randomized : 2:1
• Azacitidine (75mg/m2 D1-7) plus venetoclax ( 400 mg D1-28)
• Azacitidine + placebo

20. • Phase 3, randomized, double blind study
• Dose of venetoclax = 600 mg, prior HMA use
Median follow up = 17.5 months
1. OS = 8.4 mts vs 4.1 mts
2. EFS = 4.9 mts vs 2.1 mts
3. CR rates= 48 % vs 15%

21. 10 day decitabine
• 21 patients with TP53 mutations
• 20 mg/m2 X 10 days
• All patients have morpho < 5% blasts in BMA
• CR = 19%
N Engl J Med. 2016;375:2023-2036

22. Phase 2 trial
Decitabine 20 mg/m2 D1-10
Venetoclax 400 mg OD
Intensive chemotherapy: > 1 gm/m2/ day of AraC (2000-2018)
Favourable cytogenetics were excluded
TRM scores are used to assess

23. • DEC10-VEN shows superior outcomes compared to IC
in older pts with AML
• Benefits were most pronounced in pts at high risk of
TRM.

24. CR

25. MRD
• Done after achievement of CR/ consolidation
• Higher rates of relapse at 1 year
• Favourable risk (40% vs 5%)
• Intermediate risk (60% vs 20%)
• Poor Risk (100% vs 50%)

26. Consolidation therapy
• HIDAC 3 gm/m2 BD Day 1,3,5
• 4 year RFS OS = 44%
CBF-AML = 78%
NK-AML = 40%
Poor-cytogenetics = 21%
• German-Austrian AML group : Day 1,2,3
• ANC recovery = Shorter by 4 days
• Platelet transfusion = less