Acute Myeloid Leukemia is a clonal expansion of myeloid blasts in the blood, bone marrow, and other tissues. The median age is 68 years. Our data on 407 patients showed a median age of 29 years, with 27% pediatric cases. Good risk patients were 21%, intermediate risk 69%, and poor risk 10%. The overall complete remission rate was 70% and median overall survival was 23.8 months. New targeted therapies like midostaurin, CPX-351, venetoclax, and decitabine have shown improved outcomes compared to standard chemotherapy, especially in older or unfit patients. Monitoring for minimal residual disease after remission can help predict relapse risk.

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