Updates For Haploidentical Hematopoietic Transplantation Outcomes
Updates For Haploidentical Hematopoietic Transplantation Outcomes
Updates For Haploidentical Hematopoietic Transplantation Outcomes
Hematopoietic Transplantation
Outcomes
Piyanuch Kongtim, MD
Division of Hematology
Department of Internal Medicine
Faculty of Medicine
Thammasat University
Disclosure Information
Piyanuch Kongtim, MD
Parents
A B C D
Progeny
A C A D B R B C B D
Historical Perspective
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Powles RL, et al. Lancet 1983; 1: 612
From complete to partial ex vivo
T cell depleted HaploSCT
T-cell Depleted Haploidentical SCT
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Berenbaum MC, Brown IN. Nature. 1963;200:84.
Santos GW, Owens AH. Bull Johns Hopkins Hosp. 1965;116:327-340.
Luznik L, et al. Blood. 2001;98:3456-3464.
Mechanism Post-transplant Cyclophosphamide
1.0 1.0
0.8 0.8
0.7
50% 0.7
0.6 0.6
TCR Overall
0.5 0.5
0.4
0.4
0.3
0.3
21% TCD Remission
0.2
0.2
TCD Overall
0.1
0.1
0.0
0.0 0 2 4 6 8 10 12 14 16 18 20 22 24
0 2 4 6 8 10 12 14 16 18 20 22 24
Months Post Transplant
Months Post Transplant
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Ciurea SO, et al. Biol Blood Marrow Transplant. 2012;18:1835
NRM (left) and Mortality from Infectious
Complications (right)
1.0
1.0 P at 1yr 0.03 P at 2 yrs 0.01
0.9
0.7
0.6
0.6
0.5
0.5
TCD, N=33, 42% 0.4
0.4
0.3
TCD, 24%
0.3
0.2
0.2
TCR, N=32, 16% 0.1 TCR, 9%
0.1
0.0
0 10 20 30 40 50 60 70 80
0.0
0 10 20 30 40 50 60 70 80 90 Months Post Transplant
Months Post Transplant
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Ciurea SO, et al. Biol Blood Marrow Transplant. 2012;18:1835
Gr. II-IV aGVHD and cGVHD
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Ciurea SO, et al. Biol Blood Marrow Transplant. 2012;18:1835
Haploidentical Transplantation for
Myeloid and Lymphoid
Malignancies
Reference Conditioning regimen Diseases No. Graft aGVHD NRM Relapse PFS
pts (II-IV) rate
MYELOID
MALIGNANCIES*
Bashey A, et al. Bu/Flu/Cy regimen AML 32% 53 BM 30% 7% at 33% at 60% at
Fludarabine 25mg/m2 on days -6 to -2 (total 125 MDS/MP 60% 1yr 2yrs 2yrs
JCO. mg/m2) D 15%
2013;31:1310 Busulfan 110-130mg/m2/day IV on days -7 to -4 ALL 19%
Cyclophosphamide 14.5 mg/kg days -3 and -2
(total 29mg/kg)
Raiola A, et al. Thio/Bu/Flu regimen AML 50% 35 BM 12% 18% at 26% at 18 51% at
Thiotepa 5mg/kg on days -6 and -5 (total ALL 25% 18 mo mo 18 mo
BBMT.2013:19:1 10mg/kg) MPD 16%
17. Busulfan 3.2 mg/kg IV on days -4 to -2 (total
9.6mg/kg)
Fludarabine 50mg/2 on days -4 to -2
Flu/TBI regimen 15
TBI 3.3 Gy on days -8 to -6 (total 9.9 Gy);
Fludarabine 30mg/m2 on days -5 to -2 (total
120mg/m2)
LYMPHOID
MALIGNANCIES
Burroughs et al. Flu/Cy/TBI 200 HD 100% 28 BM 43% 9% at 40% at 51% at
BBMT. Fludarabine 30 mg/m2/day on days 6 2yrs 2yrs 2yrs
to 2
2008;14:1279
Cyclophosphamide 14.5 mg/kg/day
on days 6 and 5
2 Gy TBI on day 1.
Castagna et al. Flu/Cy/TBI 200 HD 55% 49 BM 26% 16% 19% at 65% at
BMT.2014 Fludarabine 30 mg/m2/d IV daily on NHL 39% at 2yrs 2yrs
days 6 to 2 2yrs
Cyclophosphamide 14.5 mg/kg IV on
days 6 and 5 and
2 Gy TBI on day 1
Kanakry JA, et al. Flu/Cy/TBI, Flu/TBI PTCL 100% 22 BM 16% 11% 34% at 1 40% at 2
BBMT. at 1 yr yr yrs**
2013;19:602
Kasamon Y, et al. Flu/Cy or Flu/Cy/TBI NHL 75% 151 BM 32% 16% 31% at 40% at
Fludarabine 30 mg/m2 on days -6 to HD 25% at 1yr 1yr 3yrs
-2
2 Gy TBI on day -1
Piyanuch Kongtim, Ravi Pingali, Antonio M. Jimenez, Roberto Ferro, Gabriela Rondon, Julianne Chen,
Oran Betul, Aimee Hammerstrom, Lindsey Lombardi, Partow Kebriaei, Martin Korbling, Uday R. Popat,
Simrit Parmar, Dean A Lee, Laurence Cooper, Katayoun Rezvani, Issa Khouri, Elizabeth J. Shpall, Richard
E. Champlin, Stefan O. Ciurea
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center,
Houston, TX
Patients and Methods
We retrospectively analyzed the outcomes of 100 patients
who underwent haploSCT for various hematologic
malignancies between September 2009 to July 2012 at the
university of Texas MD Anderson Cancer Center.
Various 77% vs. 100% v. 14% v. 15% v. 17% v. 18% v. 60% Raiola A.
HM 72% 60% 21% 22% 26% at 4 20% v.35% at BBMT.
MA BM yrs at 4 yrs 4 yrs 2014
MAC:
Similar characteristics with regards to age at transplant, disease status,
secondary AML, time diagnosis to transplant
Source of stem cells - BM for haploidentical transplants (82%) and PB
for MUDs (81%)
RIC:
MUD transplants older (median 62 vs. 57 yrs, p<0.001), more likely to
have a PS< 90% (41% vs. 26%, p=0.03)
MUD transplants: more in CR1 (61% vs. 49%, p<0.001) an shorted
interval diagnosis to transplant ( 12 mo, 77% vs. 65%, p=0.01)
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Leukemia Free Survival
Adjusted for DRI, performance score, secondary AML
100
Myeloablative Reduced Intensity 100
80 80
Probability, %
40 40
HAPLO 41% (32-51)
HAPLO 35% (25-45)
20 20
HR 0.98 (95% CI 0.75-1.27), p=0.87 HR 0.98 (95% CI 0.74-1.30), p=0.89
0 0
0 1 2 3 0 1 2 3
Years Years
Ciurea SO, et al. Blood 2015
Relapse
Adjusted for DRI, performance score, secondary AML
100
Myeloablative Reduced Intensity 100
40 40
MUD 42% (38-45)
MUD 39% (37-42)
20 20
0 0
0 1 2 3 0 1 2 3
Years Years
Ciurea SO, et al. Blood 2015
Non Relapse Mortality
Adjusted for performance score, DRI
100
Myeloablative Reduced Intensity 100
80 80
Cumulative Incidence, %
60 60
40 40
80 80
Cumulative Incidence, %
20 20
HAPLO 21% (14-30) HAPLO 25% (17-34)
0 0
0 3 6 9 12 0 3 6 9 12
Months Months
Ciurea SO, et al. Blood 2015
Chronic Graft vs. Host Disease
Myeloablative Reduced Intensity
100 100
40 40
0 0
0 1 2 3 0 1 2 3
Years Years
Ciurea SO, et al. Blood 2015
Haploidentical vs identical-sibling transplant for AML
in remission: a multicenter, prospective study (China)
Stefan O Ciurea, MD
Richard E. Champlin, MD
Kai Cao, PhD (HLA lab)
Milton Denai (Biostatistics)
Peter Thall, PhD (Biostatistics)
Dean Lee, MD, PhD (NK cells)
Laurence Cooper, MD and Partow Kebriaei, MD (CAR T cells)
Antonio Di Stasi, MD, PhD (Fellow)