1. Current Status of Acute Myeloid Leukemia in China Jianxiang Wang Institute of Hematology Hospital of Blood Disease Chinese Academy of Medical Sciences

2. Shen Y et al. Blood 2011;118:5593-5603 CharacteristicsAML without prognostic cytogenetic markers (group) CBF leukemiasAPL Sex.no.of patients(%) Male348(29.4)104(8.8)199(16.8) Female257(21.7)72(6.1)189(15.9) Mean age, y43.2+18.931.4+19.534.7+17.1 Range18-8618-7518-80 N0.of the patients<60 481160354 Median WBC count,10 9 /L 13.35(0.5-453)10.05(0.8- 177.9) 2.9(0.3- 205.7) Median BM blasts,%69(22.5-97)60(23.5-91)64(22.5-91.0) AML Prognosis Factors (Shang Hai/Zhe Jiang Institute of Hematology ）

3. Shen Y et al. Blood 2011;118:5593-5603 CROSEFS variables P OR(95%CI) P P Age <.001 0.976(0.966-0.987) <.001 1.018(1.011- 1.027) <.001 1.013(1.006-1.02) WBC count.02 0.996(0.992-0.999).022 1.002(1.000- 1.004).044 BM balsts NS. FLT ITD/TKDNS. C-KIT NS. N-RAS NS. NPM1+/DNMT3A -.001 2,533(1.43-4.488).014 0.626(0.431-0.91).012 0.638(0.45-0.906) Bi-CEBPA 0.005 2.45(1.319-4.553) <.001 0.396(0.214-0.65).001 0.488(0.319-0.746) WT1 NS. ASXL1 NS. DNMT3A.036 0.486(0.248-0.953).005 1.753(1.189- 2.583).010 1.638(1.123-2.388) MLL NS..002 1.803(1.240- 2.623).004 1.642(1.167-2.311) IDH1 NS. TET2 NS. 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. Induction therapy  HAA HHT 2mg/ m 2 /d d1-7 Acla 20mg /d d1-7 Ara-C 100mg/ m 2 /d d1-7  HAD: HHT 2mg/ m 2 /d d1-5/7 DNR 40 mg/ m 2 /d d1-3 Ara-C 100 mg/ m 2 /d d1-7  DA: DNR 40/45mg/ m 2 /d d1-3 Ara-C 100mg/m 2 /d d1-7 HHT -based induction therapy for patients of de novo AML （ from multicenter randomized controlled trial )

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

8. Number(%)P-value DA(N=202)HAA(N=200)HAD(N=194)HAA:DAHAD:DA 1-cycle 109(54.0%)135(67.5%)126(64.9%)0.0050.026 2-cycle 125(61.9%)150(75%)133(68.6%)0.0050.163 CR Rate

9. Group median range Group median range Group 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 OS EFS 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 RFS Survival

10. 诱导方案对低 / 中危险组的影响 EFS os HAA:DA P=0.017 HAD:DA P=0.814 HAA:DA P=0.001 HAD:DA P=0.368 HAA:DA P=0.030 HAD:DA P=0.530 RFS Group median range Group median range Group 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 Survival Patients with favorable/intermediate cytogenetic profile

11. os EFS HAA:DA P=0.059 HAD:DA P=0.760 HAA:DA P=0.424 HAD:DA P=0.973 RFS HAA:DA P=0.058 HAD:DA P=0.421 Group median range Group median range Group 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 Patients with poor cytogenetic profile

12. DA (n=205)HAA (n=206)HAD (n=198) No.(%) P （ vs.DA ） No.(%) P （ vs.DA ） Hemorrhage13/193(6.7%)10/191(5.2%)0.53615/186(8.1%)0.621 Hepatic3/192(1.6%)5/189(2.6%)0.5004/185(2.2%)0.719 Renal0/193(0)0/187(0)-0/183(0)- Cardiac0/193(0)3/188(1.6%)0.1193/185(1.6%)0.116 Gastrointestinal9/184(4.9%)12/182(6.6%)0.48411/172(6.4%)0.538 Infection (0-4)144/186(77.4%)156/188(83.0%)0.177141/178(79.2%)0.678 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) ×10 9 /L, median HGB 81(36-162)g/l ， median PLT 35(3-415)×10 9 /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.  Induction therapy HHT 2mg/ ㎡ /d d1-7 HAD group HHT 2mg/ ㎡ /d d1-7 Ara-c 100mg/ ㎡ /d d1-7 Ara-c 100mg/ ㎡ /d d1-7 DNR 40mg/ ㎡ /d d1-3 DNR 40mg/ ㎡ /d d1-3 ID-HAD group HHT 2mg/ ㎡ /d d1-7 ID-HAD group HHT 2mg/ ㎡ /d d1-7 Ara-c 100mg/ ㎡ /d d1-4, 1g/ ㎡ /q12h d5-7 Ara-c 100mg/ ㎡ /d d1-4, 1g/ ㎡ /q12h d5-7 DNR 40mg/ ㎡ /d d1-3 DNR 40mg/ ㎡ /d d1-3  Early consolidation therapy Ara-c 3.0g/ ㎡ /q12h d1-3 3 cycles HD-Ara-C group Ara-c 3.0g/ ㎡ /q12h d1-3 3 cycles ID-Ara-C group DNR 40mg/ ㎡ /d d1-3 Ara-c 1.5g/ ㎡ /q12h d1-3 ID-Ara-C group DNR 40mg/ ㎡ /d d1-3 Ara-c 1.5g/ ㎡ /q12h d1-3 MTZ 8mg/ ㎡ /d d1-3 Ara-c 1.5g/ ㎡ /q12h d1-3 MTZ 8mg/ ㎡ /d d1-3 Ara-c 1.5g/ ㎡ /q12h d1-3  Late consolidation therapy HHT 2.5mg/ ㎡ /d 1-6 Ara-c 1-6 HA HHT 2.5mg/ ㎡ /d d 1-6 Ara-c 100mg/ ㎡ /d d 1-6 continuous 2 cycles continuous 2 cycles MA MTZ 8mg/ ㎡ /d d1-3 100mg/ ㎡ /d d1-6 MA MTZ 8mg/ ㎡ /d d1-3 Ara-c 100mg/ ㎡ /d d1-6 continuous 1-2 cycles continuous 1-2 cycles R R

18. Risk category (based on cytogenetics and molecular abnormalities) Risk statuscytogeneticsMolecular abnormalities better-risk inv(16) t(8;21) t(16;16) normal cytogenetics: with NPM1 mutation or isolation CEBPA mutation in the absence of FLT3-ITD Intermediate-risk Normal +8 、 t(9;11) Other non-defined t(8;21), inv(16), t(16;16) with c-KIT mutation Poor-risk complex(  3 clonal chromosomal abnormalities ) － 5, － 7,5q-7q-,11q23 non t(9;11), Inv(3), t(3;3), t(6;9), t(9;22) Normal cytogenetics With FLT3-ITD mutation

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

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

21. D. Description of the contents 2 years OS rate 62% 2 years RFS rate70% 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 Survival

22. Poor intermediate 低危组 favorable P=0.0P=0.015 favorable intermediate Poor Death(N.) 6/74 18/76 17/47 2 years OS rate 80% 58% 43% favorable intermediate Poor Relapse(N.) 6/70 10/58 8/29 2 years DFS rate 76% 71% 52% Survival Risk groups Cum survival OS(months ） favorable intermediate Poor Cum survival RFS(months ）

23. D. Description of the contents SD-Ara-c group ID-Ara-c group Death(N.) 21/101 20/96 2 years OS rate 55% 67% SD-Ara-c group ID-Ara-c group Relapse(N.) 11/73 13/84 2 years RFS rate 62% 76% Cum survival OS(months ） ID-Ara-c induction group SD-Ara-c induction group P=0.491 P=0.773 ID-Ara-c induction group SD-Ara-c induction group Cum survival RFS(months ） Induction therapy Survival

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

25. D. Description of the contents Survival HD-Ara-c group ID-Ara-c group HD-Ara-c ID-Ara-c Death (N.) 11/75 8/70 2 years OS rate 71% 76% HD-Ara-c ID-Ara-c Replase (N.) 15/75 9/62 2 years DFS rate 61% 78% consolidation therapy P=0.404 ID-Ara-c group HD-Ara-c group Cum survival Os (months) P=0.191 Cum survival RFS (months)

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

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

28. ID-Ara-C （ n=98 ） SD-Ara-C （ n=103 ） Induction Related Mortality 6 （ 6.1%) 1(0.97%) P>0.05 the lowest WBC count （ ×10 9 /L ） 0.07 （ 0.01-0.38 ） 0.23 （ 0.02-1.44 ） P =0.0 WBC< 1×10 9 /L continuous days 15 （ 5-28 ） 14.5 （ 6-41 ） P =0.041 infection （ n=89 ） （ n=76 ） P =0.03 3-4 Ⅱ o intestinal,crissum infection 17 （ 19.1%) 11(14.5%) 3-4 Ⅱ o oral cavity,gingiva infection 2 （ 2.2% ） 3 （ 3.9% ） 4 Ⅱ o Septicemia 18 （ 20.2% ） 9 （ 11.8% ） Liver infection 3 （ 3.3% ） 1(1.3%) 3-4 Ⅱ o lung infection 25(28.1%) 26(34.2%) 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. Than k you