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Shen Y et al. Blood 2011;118:5593-5603

Current Status of Acute Myeloid Leukemia in China Jianxiang Wang Institute of Hematology Hospital of Blood Disease Chinese Academy of Medical Sciences. AML Prognosis Factors (Shang Hai/Zhe Jiang Institute of Hematology ）. Shen Y et al. Blood 2011;118:5593-5603.

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Shen Y et al. Blood 2011;118:5593-5603

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  1. Current Status of Acute Myeloid Leukemia in ChinaJianxiang WangInstitute of Hematology Hospital of Blood DiseaseChinese Academy of Medical Sciences

  2. AML Prognosis Factors(Shang Hai/Zhe Jiang Institute of Hematology ） Shen Y et al. Blood 2011;118:5593-5603

  3. Shen Y et al. Blood 2011;118:5593-5603 CR, OS and EFS-Multivariate Analysis

  4. OS and EFS According to Genotypes -Multivariate Analysis. Shen Y et al. Blood 2011;118:5593-5603

  5. Homoharringtonine(HHT)- based induction therapy

  6. HHT -based induction therapy for patients of de novo AML（from multicenter randomized controlled trial) • Induction therapy • HAA • HHT 2mg/ m2/d d1-7 • Acla 20mg /d d1-7 • Ara-C 100mg/ m2/d d1-7 • HAD: • HHT 2mg/ m2 /d d1-5/7 • DNR 40 mg/ m2 /d d1-3 • Ara-C 100 mg/ m2 /d d1-7 • DA: • DNR 40/45mg/ m2 /d d1-3 • Ara-C 100mg/m2/d d1-7

  7. PR/(reduced blast cells≥60％) NR/(reduced blast cells<60％) CR Continued previous regimen Salvage therapy ID-Ara-C*2 CR PR/NR Withdraw from the study Observed for 3-year DA/HA，MA，DA/HA，AA Patients were randomly assigned to HAA，HAD or DA treatment groups

  8. CR Rate

  9. Survival OS EFS RFS HAA:DA P=0.584 HAD:DA P=0.979 HAA:DA P=0.003 HAD:DA P=0.091 HAA:DA P=0.115 HAD:DA p=0.220 Group median range Group median rangeGroup median range HAA 26.0 (16.3-35.7)M HAA 11.7 (8.6-14.8) M HAA 31.3 not reach M HAD 22.6 (12.3-32.9) M HAD 8.6 (5.4-11.8)M HAD 21.7 not reach M DA 21.1 (15.1-27.1)M DA 6.9 (4.0-9.8) M DA 15.5 ( 10.8-20.2)M

  10. Survival Patients with favorable/intermediate cytogenetic profile os RFS 诱导方案对低/中危险组的影响 EFS HAA:DA P=0.030 HAD:DA P=0.530 HAA:DA P=0.001 HAD:DA P=0.368 HAA:DA P=0.017 HAD:DA P=0.814 Group median range Group median rangeGroup median range HAA not reach not reach M HAA 15.2 (8.7-21.7)M HAA not reach not reach M HAD 20.6 (8.6-32.6)) M HAD 8.0 (5.1-10.9)M HAD 17.8 not reach M DA 18.4 (11.7-25.1) M DA 7.5 (5.0-9.8)M DA 15.9 ( 9.5-22.3) M

  11. Patients with poorcytogenetic profile os RFS EFS HAA:DA P=0.059 HAD:DA P=0.760 HAA:DA P=0.058 HAD:DA P=0.421 HAA:DA P=0.424 HAD:DA P=0.973 Group median range Group median rangeGroup median range HAA 7.6 (0-15.8) M HAA 2.2 (0.2-4.2) M HAA 3.8 (0.0-13.9) M HAD 17.1 (0-34.5) M HAD 2.1 (0-12.3) M HAD 11.9 not reachM DA 10.9 (4.9-17.0) M DA 1.1 (0.2-2.0) M DA not reach not reach M

  12. Adverse Events

  13. ID-Ara-C、Homoharringtonine (HHT)- based induction therapy

  14. ID-Ara-C-based induction therapy

  15. Induction of Ara-C dose effect relation Am. J. Hematol. 2009, 84:422–427.

  16. 2010.9.1- 201 de novo<55, AML patients were enrolled follow up to 2012.12.31，The median follow-up 8.85（0.33-27.67）months Male 105，Famale 96 Median age 37（15-54） At diagnosis median WBC count 12.7(0.81-275.4) ×109/L, median HGB 81(36-162)g/l，median PLT 35(3-415)×109/L HHT/ID-Ara-C-based inductin therapy for the patients of de novo AML（the data of Chinese Academy of Medical Sciences Institute of Hematology)

  17. R R • Induction therapy • HAD groupHHT 2mg/㎡/d d1-7 Ara-c 100mg/㎡/d d1-7 DNR 40mg/㎡/d d1-3 • ID-HAD groupHHT 2mg/㎡/d d1-7 Ara-c 100mg/㎡/d d1-4, 1g/㎡/q12h d5-7 DNR 40mg/㎡/d d1-3 • Early consolidation therapy • HD-Ara-C groupAra-c 3.0g/㎡/q12h d1-3 3 cycles • ID-Ara-C groupDNR 40mg/㎡/d d1-3Ara-c 1.5g/㎡/q12h d1-3 MTZ 8mg/㎡/d d1-3Ara-c 1.5g/㎡/q12h d1-3 • Late consolidation therapy • HA HHT 2.5mg/㎡/dd1-6 Ara-c 100mg/㎡/dd1-6 continuous 2 cycles • MA MTZ 8mg/㎡/d d1-3Ara-c 100mg/㎡/dd1-6 continuous 1-2 cycles

  18. Risk category (based on cytogenetics and molecular abnormalities)

  19. NR n=26(25.2%) deathn=1(0.97%) no evalution n=2 CR n=74 （71.8%） Discontinue n=5 (6.7%) HD-Ara-C （n=75） SD-Ara-Cinduction （n=103） 201 AML patients （≤55 years） CR n=84 （85.7%） Discontinue n=8（9.5%） ID-Ara-C （n=70） ID-Ara-C induction （n=98） NR n=6 (6.1%) deathn=6 (6.1%) no evalution n=2

  20. Induction therapy for risk stratification 低危组 favorable induction therapy SD-Ara-C group ID-Ara-C group 97.4% 94.3% （38/39） （33/35） P>0.05 intermediate Poor induction therapy SD-Ara-C group ID-Ara-C group 40.0% 86.4% （10/25） （19/22） P<0.05 induction therapy SD-Ara-C group ID-Ara-C group 70.3% 82.1% （26/37） （32/39） P<0.05

  21. Survival Follow up to 2012.12.31, 42patients died. 7 patients died during induction therapy,19 patients died because of relapse,16 patients died after NR Follow up to 2012.12.31 24 patients relapse D. Description of the contents 2years RFSrate70% 2years OSrate 62%

  22. Survival Risk groups 低危组 favorable favorable Cum survival Cum survival intermediate intermediate Poor Poor P=0.0 P=0.015 RFS(months） OS(months） favorableintermediatePoor Relapse(N.)6/7010/588/29 2yearsDFSrate 76% 71% 52% favorableintermediatePoor Death(N.)6/7418/7617/47 2yearsOSrate80% 58% 43%

  23. Survival Induction therapy ID-Ara-c induction group ID-Ara-c induction group Cum survival Cum survival SD-Ara-c induction group SD-Ara-c induction group P=0.773 P=0.491 RFS(months） OS(months） D. Description of the contents SD-Ara-c group ID-Ara-c group Death(N.)21/10120/96 2years OSrate55% 67% SD-Ara-c group ID-Ara-c group Relapse(N.)11/7313/84 2years RFSrate62% 76%

  24. Survival Induction therapy D. Description of the contents Poor-risk Better-risk Intermediate-risk ID-Ara-C induction group ID-Ara-C induction group Cum survival ID-Ara-C induction group Cum survival Cum survival SD-Ara-C induction group C. Description of the contents SD-Ara-C induction group SD-Ara-C induction group P=0.75 P=0.815 P=0.11 Os (months) Os (months) Os (months)

  25. Survival consolidation therapy D. Description of the contents ID-Ara-c group ID-Ara-c group Cum survival Cum survival HD-Ara-c group HD-Ara-c group P=0.191 P=0.404 Os (months) RFS (months) HD-Ara-c ID-Ara-c Death (N.) 11/758/70 2 years OS rate71% 76% HD-Ara-c ID-Ara-c Replase (N.) 15/759/62 2 years DFS rate61% 78%

  26. Survival consolidation therapy Poor-risk Better-risk Intermediate-risk ID-Ara-c group HD-Ara-c group Cum survival HD-Ara-c group Cum survival Cum survival HD-Ara-c group ID-Ara-c group ID-Ara-c group P=0.358 P=0.082 P=0.885 Os (months) Os (months) Os (months)

  27. Survival Induction, consolidation therapy Intermediate-risk Poor-risk Better-risk SD-Ara-C / HD-Ara-C group ID-Ara-c / HD-Ara-C group ID-Ara-C /ID-Ara-C group SD-Ara-C/HD-Ara-C group Cum survival ID-Ara-c / HD-Ara-C group Cum survival Cum survival ID-Ara-C /ID-Ara-C group ID-Ara-C /ID-Ara-C group SD-Ara-C / ID-Ara-C group SD-Ara-C / ID-Ara-C group SD-Ara-C / ID-Ara-C group ID-Ara-c / HD-Ara-C group SD-Ara-C/HD-Ara-C group P=0.108 P=0.83 P=0.014 Os (months) Os (months) Os (months)

  28. Adverse Events

  29. Summary Currently, major hematological centers in China has been established diagnosis and classification system of AL based cytogenetics and molecular genetics. The therapy of AML in China has achieved dramatic progress, improved long -term survival of AML patients substantially. Cooperative groups are required for clinical trials.

  30. Thank you

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