- Dr. Xiao Jun Huang is a pioneer in haploidentical stem cell transplantation and leads the transplant program at Peking University. - Allogeneic hematopoietic stem cell transplantation from a matched related donor or matched unrelated donor is preferred for intermediate and high risk AML in first remission. Haploidentical stem cell transplantation may also benefit these patients. - For favorable risk AML in first remission, patients with minimal residual disease-defined high risk may benefit from allogeneic stem cell transplantation. - Some patients over age 60 with intermediate and high risk AML in first remission could benefit from reduced-intensity allogeneic stem cell transplantation or microtransplant

1. XIAO JUN HUANG, MD, PHD
Beijing, China
• Chairman, Peking University Institute of Hematology;
Director, Department of Hematology, Peking University
People’ s Hospital; Director, Beijing Key Laboratory of
Hematopoietic Stem Cell Transplantation
• Dr. Xiao Jun Huang, MD, PhD is a pioneer in the field of
haploidentical stem cell transplant and leads the transplant
program at Peking University. As the Head of the
Association of Chinese Hematologists, five years ago, Dr.
Huang established a platform of education for professional
standardization to junior hematologists in Mainland China. It
consists of series of conference that covers around 20 cities
each year in China. He serves as APHCON
President/Executive Chairman and is committed to uniting
practicing hematologists of participating nations and
providing educational opportunities to the younger
generation. He also serves as the President of the
Chinese Society of Hematology.

2. Hematopoietic stem cell
transplantation for the treatment of
acute myeloid leukemia in CR1: who
and which type
Xiao-Jun Huang
Peking University People’s Hospital
& Institute of Hematology
Beijing Key Laboratory of HSCT

3. NCCN guideline for AML

4. 0
1000
2000
3000
4000
19641982198419861988199019921994199619982000200220052007200920112013
0
200
400
600
800
1000
1200
1400
1600
1800
2000
1990 1996 2002 2004 2006 2008 2010 2012
Number of HSCT cases in PUIH

5. Dose allogeneic hematopoietic stem cell transplantation
benefit all patients with AML in CR1 ? Who and wich type?
AML-CR1
≤60 ys
Favorable
risk
Unfavorable
risk
＞60ys
Favorable
risk
Unfavorable
risk
Is allo-HSCT benefit
for the different age
group
Is allo-HSCT benefit
for the favorable risk
AML in CR1
Which type of HSCT
will be chosen?

6. HSCT for patients aged ＜60 years old

7. HSCT for unfavorable risk AML in CR1
• Does patients with intermediate- or high risk
AML in CR1 benefit from allogeneic HSCT?
• Which type of allogeneic HSCT will be chosen?

8. By treatment arm for the
unfavorable risk group
E3489/S9034
Blood. 2000 Dec 15;96(13):4075-83.
A single phase III intergroup study

9. J Clin Oncol. 2011 Jul 10;29(20):2758-65.
1996-2005;
N=1557;
Southern German Hemoblastosis Group
AML96 trial
OS in patients without allogeneic SCT was generally worse
than in patients who received an allogeneic SCT

10. HOVON-SAKK
Leukemia (2014), 1–10

11. OS was comparable following allo HSCT and auto HSCT in patients with
intermediate-risk. Allo HSCT was associated with less relapse (hazard
ratio (HR) 0.51, P＜0.001) and better relapse free survival (RFS) (HR 0.74
P = 0.029) as compared with auto HSCT in intermediate-risk AMLs
Leukemia (2014), 1–10
HOVON-SAKK

12. Meta-analysis of prospective clinical trials
JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)

13. Meta-analysis of prospective clinical trials
JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)

14. Summary 1
• Allogeneic HCT from a matched related donor
(MRD) or a matched unrelated donor(MUD) is a
preferred therapy for patients with intermediate
and high risk AML inCR1.

15. What about the role of
Haplo-HSCT in
intermediate and high
risk AML in CR1 ？

16. Lu DP, et al. Blood,2006,107(8):3065-3073
Haplo-HSCT vs. MSD
Unmanipulated HBMT can achieve comparable
outcomes with matched related donor transplant

17. Haplo-HSCT vs. CT
Data source: PKUH
Patients: from 2006.1-2010.5, prospective
Huang XJ, et al. Blood,2012,119(23):5584-5590

18. Superior survival of HBMT to chemotherapy alone as post-remission therapy for IR
and HR AML
Huang XJ, et al. Blood,2012,119(23):5584-5590

19. Haplo vs. MSD
Transplant Candiate
Matched sibling donor
Yes (n=219)
MSDT
NO
Unrelated donor
YesNO
MUDTHaplo-SCT (n=231)
This study was registered as ChiCTR-OCH-10000940 at www. chictr.org.

20. Manipulated haplo-SCT is a valid alternative modality
Wang Y, Huang XJ, et al. Unpublished data from a multicenter study
TRM Relapse

21. Unmanipulated haplo-SCT is a valid alternative modality
Wang Y, Huang XJ, et al. Unpublished data from a multicenter study
OS LFS
Days since transplant Days since transplant
Identical sibling donor Identical sibling donor
Haploidentical donor Haploidentical donor

22. Summary 2
• Haplo-hematopoietic cell transplantation may
benefit patients with intermediate and high
risk AML in CR1

23. Transplant candidate of AML
HLA-identical related donors
Yes
MSDT
No
1. Search 8/8 matched unrelated
donor with 8 week?
2. Urgent for transplantion?
not urgent
8/8 MUDTHaplo-SCT
urgent
Huang XJ, et al. Blood,2012,119(23):5584-5590 Lu DP, et al. Blood,2006,107(8):3065
Chang YJ,et al. Semin Oncol,2012,39:653-663 Mo XD, et al. BMT,2014,Online publication
Recommendation 1

24. NCCN-2015
No room of
allo-HSCT
Is all patients with
favorable risk
factor will have a
favorable outcome?

25. UK MRC-AML15
Liu Yin JA ,et al . Blood 2012; 120: 2826
MRD analysis in a perspective protocol MRC-AML15
Time : 2002.7 -2009.1
Including: 361 CBF-AML 278 suitable for MRD study t(8;21) N=163
MRD monitoring: CR、each consolidation、follow-up
CR: >3log
Post-consolidation 3:>4log
Follow-up: BM>500copies
t(8;21)（n=59)

26. • Prospective, multicenter,
cohort study
• Time :from 2005.6 to 2011.11
• MRD: RUNX1-RUNX1T1( RQ-
PCR )
• KIT mutation: direct
sequencing
Huang XJ, et al. Blood 2013; 121 4056
AML05 trial: MRD-directed
stratification treatment of t(8;21)-AML

27. High-risk(MRD): CT vs. HSCT
Huang XJ, et al. Blood 2013; 121 4056

28. Multivariate analysis
CIR DFS OS
p p p
MRD status
high- vs. low-risk 0.003 0.002 0.02
Treatment choice
risk- vs. non risk-directed 0.026 0.036 0.037
KIT status
mutation vs. wild-type 0.049 ns ns
Huang XJ, et al. Blood 2013; 121 4056

29. Allo-HSCT can improve outcome
of high-risk t(8;21)AML

30. MRD could predict relapse in AML with inv(16)
or t(16;16)
IS allo-HSCT can improve outcome of high-risk
inv (16) or t(16;16) AML?

31. MRD post Consolidation ≤0.2%
MRD post Cons 1 ≤0.2%
MRD post Cons 2 ≤0.2%
Unpublished data of PUIH

32. Allo-HSCT can improve outcome of high-risk
inv(16)AML
MRD post Cons 2 >0.2%
MRD post Cons 2 >0.2% or lose ≤0.2% post Cons3-8
Unpublished data of PUIH

33. Recommendation 2
• Patients with MRD-stratified high risk AML
with t(8;21), inv (16) or t(16;16) may benefit
from the allogeneic HSCT.
• Prospective studies are need to confirm the
conclusion

34. HSCT for patients aged ≥60 years old

35. HSCT or CT ,
which will be
chosen?

36. Allo HSCT or CT
• 1999-2006, retrospective, matched
• Allo-HCT patients (n=94) (excluding UCB
and MAC) from CIBMTR aged 60-70
• CT patients (n=96) from two
CALGB( CALGB 9720 and CALGB19902)
• All patients included had been in CR1 for
at least 4 months
3-year NRM 36% vs. 4%; P＜0.01
3-year relapse 32% vs. 81%; P＜0.01
3-year LFS 32% vs. 15%; P＜0.01 3-year OS 37% vs. 25%; P=0.08
Biol Blood Marrow Transplant 17:1796-1803, 2011

37. Blood. 2007 Feb 15;109(4):1395-400. Epub 2006 Oct 12.
There is still no study compared RIC
with MAC HSCT for elderly patients
RIC-HSCT was superior than CT(P = .004)

38. Micro transplantation(MST)
Blood. 2011 Jan 20;117(3):936-41
G-PBSC infusion improves the
probability of DFS and OS for
elderly patients with AML.
2-years DFS (MST vs. control)
38.9% vs. 10% P=0.01
2-years OS (MST vs. control)
39.3% vs. 10.3% P=0.0006

39. Micro transplantation(MST)
6-year leukemia-free survival (LFS) 6-year overal survival (OS)
Low-risk group 84.4% 89.5%
Intermediate-risk group 59.2% 65.2%
P=0.272
P=0.308
No GVHD was observed in any of the patients
Micro transplantation as a post remission therapy may improve
outcomes and avoid GVHD in patients with AML-CR1
J Clin Oncol. 2012 Nov 20;30(33):4084-90.

40. Summary 3
• Some patients aged ＞60 years old with
intermediate and high risk AML in CR1 could
benefit from allogeneic HSCT.
• RIC conditioning regimen is preferred and micro
transplantation may be a choice.

41. Conclusions
AML patients in CR1
Intermediate risk
and/or high risk
Favorable risk
ECOG PS 0-1
And elects aggressive treatment
CR1
Allo HSCT
MRD stratified high risk
group

42. Thank you for your attention!
Stem cell collection center
Hai-Yin Zheng
Hong Xu
Qing Zhao
Su Wang
Department of bone marrow transplant
Xiao-Jun Huang Dai-Hong Liu
Kai-Yan Liu Xiao-Su Zhao
Lan-Ping Xu Xiao-Hui Zhang
Huan Chen Wei Han
Xiang-Yu Zhao Yu-Hong Chen
Feng-Rong Wang Yu Wang
Jing-Zhi Wang Chen-Hua Yan
Yuan-Yuan Zhang Yu Ji
Yu-Qian Sun
Laboratory of PUIH
Dan Li
Ya-Zhen Qin
Yan-Rong Liu
Yue-Yun Lai