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XIAO JUN HUANG, MD, PHD
Beijing, China
• Chairman, Peking University Institute of Hematology;
Director, Department of Hema...
Hematopoietic stem cell
transplantation for the treatment of
acute myeloid leukemia in CR1: who
and which type
Xiao-Jun Hu...
NCCN guideline for AML
0
1000
2000
3000
4000
19641982198419861988199019921994199619982000200220052007200920112013
0
200
400
600
800
1000
1200
140...
Dose allogeneic hematopoietic stem cell transplantation
benefit all patients with AML in CR1 ? Who and wich type?
AML-CR1
...
HSCT for patients aged <60 years old
HSCT for unfavorable risk AML in CR1
• Does patients with intermediate- or high risk
AML in CR1 benefit from allogeneic HS...
By treatment arm for the
unfavorable risk group
E3489/S9034
Blood. 2000 Dec 15;96(13):4075-83.
A single phase III intergro...
J Clin Oncol. 2011 Jul 10;29(20):2758-65.
1996-2005;
N=1557;
Southern German Hemoblastosis Group
AML96 trial
OS in patient...
HOVON-SAKK
Leukemia (2014), 1–10
OS was comparable following allo HSCT and auto HSCT in patients with
intermediate-risk. Allo HSCT was associated with less...
Meta-analysis of prospective clinical trials
JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)
Meta-analysis of prospective clinical trials
JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)
Summary 1
• Allogeneic HCT from a matched related donor
(MRD) or a matched unrelated donor(MUD) is a
preferred therapy for...
What about the role of
Haplo-HSCT in
intermediate and high
risk AML in CR1 ?
Lu DP, et al. Blood,2006,107(8):3065-3073
Haplo-HSCT vs. MSD
Unmanipulated HBMT can achieve comparable
outcomes with match...
Haplo-HSCT vs. CT
Data source: PKUH
Patients: from 2006.1-2010.5, prospective
Huang XJ, et al. Blood,2012,119(23):5584-5590
Superior survival of HBMT to chemotherapy alone as post-remission therapy for IR
and HR AML
Huang XJ, et al. Blood,2012,11...
Haplo vs. MSD
Transplant Candiate
Matched sibling donor
Yes (n=219)
MSDT
NO
Unrelated donor
YesNO
MUDTHaplo-SCT (n=231)
Th...
Manipulated haplo-SCT is a valid alternative modality
Wang Y, Huang XJ, et al. Unpublished data from a multicenter study
T...
Unmanipulated haplo-SCT is a valid alternative modality
Wang Y, Huang XJ, et al. Unpublished data from a multicenter study...
Summary 2
• Haplo-hematopoietic cell transplantation may
benefit patients with intermediate and high
risk AML in CR1
Transplant candidate of AML
HLA-identical related donors
Yes
MSDT
No
1. Search 8/8 matched unrelated
donor with 8 week?
2....
NCCN-2015
No room of
allo-HSCT
Is all patients with
favorable risk
factor will have a
favorable outcome?
UK MRC-AML15
Liu Yin JA ,et al . Blood 2012; 120: 2826
MRD analysis in a perspective protocol MRC-AML15
Time : 2002.7 -200...
• Prospective, multicenter,
cohort study
• Time :from 2005.6 to 2011.11
• MRD: RUNX1-RUNX1T1( RQ-
PCR )
• KIT mutation: di...
High-risk(MRD): CT vs. HSCT
Huang XJ, et al. Blood 2013; 121 4056
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-...
Allo-HSCT can improve outcome
of high-risk t(8;21)AML
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;1...
MRD post Consolidation ≤0.2%
MRD post Cons 1 ≤0.2%
MRD post Cons 2 ≤0.2%
Unpublished data of PUIH
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...
Recommendation 2
• Patients with MRD-stratified high risk AML
with t(8;21), inv (16) or t(16;16) may benefit
from the allo...
HSCT for patients aged ≥60 years old
HSCT or CT ,
which will be
chosen?
Allo HSCT or CT
• 1999-2006, retrospective, matched
• Allo-HCT patients (n=94) (excluding UCB
and MAC) from CIBMTR aged 60...
Blood. 2007 Feb 15;109(4):1395-400. Epub 2006 Oct 12.
There is still no study compared RIC
with MAC HSCT for elderly patie...
Micro transplantation(MST)
Blood. 2011 Jan 20;117(3):936-41
G-PBSC infusion improves the
probability of DFS and OS for
eld...
Micro transplantation(MST)
6-year leukemia-free survival (LFS) 6-year overal survival (OS)
Low-risk group 84.4% 89.5%
Inte...
Summary 3
• Some patients aged >60 years old with
intermediate and high risk AML in CR1 could
benefit from allogeneic HSCT...
Conclusions
AML patients in CR1
Intermediate risk
and/or high risk
Favorable risk
ECOG PS 0-1
And elects aggressive treatm...
Thank you for your attention!
Stem cell collection center
Hai-Yin Zheng
Hong Xu
Qing Zhao
Su Wang
Department of bone marro...
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Allogeneic Stem cell transplant in CR1 for AML

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Allogeneic Stem cell transplant in CR1 for AML. Prof XiaoJun Huang

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Allogeneic Stem cell transplant in CR1 for AML

  1. 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. 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. 3. NCCN guideline for AML
  4. 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. 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. 6. HSCT for patients aged <60 years old
  7. 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. 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. 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. 10. HOVON-SAKK Leukemia (2014), 1–10
  11. 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. 12. Meta-analysis of prospective clinical trials JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)
  13. 13. Meta-analysis of prospective clinical trials JAMA, June 10, 2009—Vol 301, No. 22 (Reprinted)
  14. 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. 15. What about the role of Haplo-HSCT in intermediate and high risk AML in CR1 ?
  16. 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. 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. 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. 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. 20. Manipulated haplo-SCT is a valid alternative modality Wang Y, Huang XJ, et al. Unpublished data from a multicenter study TRM Relapse
  21. 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. 22. Summary 2 • Haplo-hematopoietic cell transplantation may benefit patients with intermediate and high risk AML in CR1
  23. 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. 24. NCCN-2015 No room of allo-HSCT Is all patients with favorable risk factor will have a favorable outcome?
  25. 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. 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. 27. High-risk(MRD): CT vs. HSCT Huang XJ, et al. Blood 2013; 121 4056
  28. 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. 29. Allo-HSCT can improve outcome of high-risk t(8;21)AML
  30. 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. 31. MRD post Consolidation ≤0.2% MRD post Cons 1 ≤0.2% MRD post Cons 2 ≤0.2% Unpublished data of PUIH
  32. 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. 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. 34. HSCT for patients aged ≥60 years old
  35. 35. HSCT or CT , which will be chosen?
  36. 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. 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. 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. 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. 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. 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. 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

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