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


AML Prognosis Factors(Shang Hai/Zhe Jiang Institute of Hematology )

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


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

CR, OS and EFS-Multivariate Analysis


OS and EFS According to Genotypes -Multivariate Analysis.

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


Homoharringtonine(HHT)- based induction therapy


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


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



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


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


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



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



Induction of Ara-C dose effect relation

Am. J. Hematol. 2009, 84:422–427.


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)


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


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


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


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


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%


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%


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%


Survival
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)


Survival1
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%


Survival2
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)


Survival3
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)



Summary
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.



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