HLA Haploidentical Transplantation:
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1 HLA Haploidentical Transplantation: The Journey to the Transplantation For All Kitsada Wudhikarn, MD Division of Hematology, Department of Medicine King Chulalongkorn Memorial Hospital
2 Disclosure No relevant conflict of interest to disclose
3 Outlines Introduction Major approaches of HLA haploidentical transplantation Selecting best donor for HLA haploidentical transplantation Limitation of HLA haploidentical transplantation
4 Introduction Only 3% chance of available HLA matched sibling donor (MSD) HLA matched unrelated donor considered standard after MSD Availability and accessibility to HLA identical matched unrelated donor are limited 25% chance of having HLA matched sibling
5 Obstacles in finding matched unrelated donor Diagnosis No matched donor available in national or international registries Delay in referral to transplant center or sibling typing Donors typed at low resolution and/or only at HLA-A and B loci Donor unavailable for CT/harvest or donor medically unfit for donation Lack of expertise in interpreting search report Donor unable to meet timescale set by transplant center, or withdraws at a late stage Delays in transit of HPC across international borders Transplant
6 23% Percentage Matched Likelihood of HLA-matched unrelated donor availability % 9% 8% 7% 6% 5% 4% 3% 2% 1% % 67% 12% 21% 38% 2% 42% 41% 19% 4% 12% 65% WH HIS API AFA No 1/1 Indeterminate 1/1 Dehn J et al. Biol Blood Marrow Transplant. 215 Jan;21(1): Buck K et al. Biol Blood Marrow Transplant. 216 Apr;22(4): Gragert L et al. N Engl J Med. 214 Jul 24;371(4):339-48
7 Alternative hematopoietic stem cell donors Mismatched unrelated hematopoietic stem cell donor One locus mismatch > two loci mismatch Umbilical cord blood hematopoietic stem cell HLA-haploidentical (related) hematopoietic stem cell donor
8 Percetage Matched Chance and Outcome 9/1 MMUD % 9% 8% 7% 6% 5% 4% 3% 2% 1% % 94% 6% 72% 28% 74% 26% 61% 39% WH HIS API AFA No 9/1 9/1 Kekre N et al. Am J Hematol. 216 Jun;91(6):551-5
9 Percetage Matched Chance and Outcome 9/1 MMUD % 9% 8% 7% 6% 5% 4% 3% 2% 1% 94% 6% 72% 28% 74% 26% 61% 39% No 9/1 9/1 Study Crocchiolo (29) Fürst (213) Loiseau (27) Petersdorf (HR)(24) Petersdorf (LR)(24) Robin (215) Smith (216) Walter (21) Overall (I 2 = 31.2%) HR (95% CI) 1.12 (.9,1.4) 1.26 (1.11,1.43) 1.41 (1.1,1.98) 1.9 (.86,1.38) 2.27 (1.47,3.51) 1.3 (.8,2.13) 1.29 (.43,3.89) 1.16 (.52,2.61) 1.27 (1.12,1.45) % WH HIS API AFA Favors 9/1 Favors 1/1 Kekre N et al. Am J Hematol. 216 Jun;91(6):551-5
10 Cord blood transplantation Advantages Readily available Increased availability for minorities Decreased transmission of viruses (i.e. CMV) Greater degree of HLA mismatch allowed Disadvantages One unit rescues one patient/no DLI Theoretical risk of genetic disease transmission Theoretical risk of maternal cell contamination (GVHD) Slow engraftment Expensive
11 Match likelihood Likelihood of Finding URD or CB when searching adult donor, then cord blood % 9% 8% 7% 6% 5% 4% 3% 2% 1% % Race or ethnic group of searching patient 8/8 HLA adult donor 7/8 HLA adult donor 6/6 HLA cord blood 5/6 HLA cord blood 4/6 HLA cord blood Gragert L, et al. N Engl J Med. 214; 371(4):
12 Journey of HLA haploidentical SCT Haplo BMT Modern approach to haplo SCT Allo BMT for leukemia MUD SCT TCD PTCy GIAC CD3/CD19- Treg αβcd3/cd Twin SCT Cyclosporine for GVHD UCB SCT du-ucb NiCO UCB expansion StemRegenin-1 Liu JH et al. Curr Opin Hematol. 218 Mar;25(2):13-111
13 Haploidentical SCT: Tug the war (Fighting of HLA disparity) Rejection Recipient GVHD Donor
14 Early Results High rates of graft failure & GvHD Powles RL et al. Lancet Mar 19;1(8325):612-5
15 Approaches of modern HLA haploidentical SCT T cell depleted graft Megadose HSCT approach with CD34+ selected PBSC graft (Perugia, Italy) T cell repleted graft High-dose post-transplantation cyclophosphamide (Hopkins) GIAC protocol (China)
16 T cell Depleted Haploidentical Transplantation: Perugia protocol stbi 8 Gy Thiotepa 5 mg/kg x 2 d ATG-Fresenius 25 mg/kg over 5 days or Thymoglobulin 6 mg/kg over 5 days TCD PBSC infusion Day Fludarabine 4 mg/m 2 x 5 days No agvhd prophylaxis Megadose T cell depleted CD34+ cells BM + G-CSF stimulated PBSC: Ensure engraftment 95% achieved engraftment with minimal agvhd & cgvhd (No GVHD prophylaxis) Aversa F et al. Blood Dec 1;84(11): Aversa F et al. N Engl J Med. 1998;339:
17 T cell Depleted Haploidentical Transplantation: Perugia protocol stbi 8 Gy Thiotepa 5 mg/kg x 2 d ATG-Fresenius 25 mg/kg over 5 days or Thymoglobulin 6 mg/kg over 5 days TCD PBSC PBSC infusion CD3+ cells < 2x1 4 cells/kg Day Fludarabine 4 mg/m 2 x 5 days No agvhd prophylaxis Megadose T cell depleted CD34+ cells BM + G-CSF stimulated PBSC: Ensure engraftment 95% achieved engraftment with minimal agvhd & cgvhd (No GVHD prophylaxis) Aversa F et al. Blood Dec 1;84(11): Aversa F et al. N Engl J Med. 1998;339:
18 Cumulative incidence Cumulative incidence TCD haploidentical transplant: Non Relapse mortality ALL (n=37) Any remission (n=24) Relapse (n=13) Relapse (n=25) AML (n=67) Any remission (n=42) Months 38/11 death in remission: Infection is the leading cause of death Low agvhd and cgvhd but high transplant related mortality Months Aversa F et al. J Clin Oncol. 25 May 2;23(15):
19 Immune cell components of graft PBSC CD34+ (progenitor cells) CD3+ (T cells) CD19+ (B cells) CD56+ (NK cells) CD14+ (Dendritic cells) αβ T cells 95% γδ T cells 5% Treg (CD4+/CD25 +/FOXP3+) CD4+ Naïve T cell (CD45RA+) CD8+ Yellow text = innate immune cell components of the graft
20 Graft manipulation strategy in TCD haplo SCT Depletion (targeted negative selection) Pan T-cell depletion Lymphocyte subset depletion CD8+ T-cell depletion CD3/CD19 cell depletion αβ T-cell/CD19 cell depletion (Germany-Italy Approach) Naïve T-cell depletion Inclusion (positive selection/expansion add back): Treg cells, Tcon cells, NK cells, γδ T cells
21 CliniMACs cell separator system Immuno-magnetic microbead Biotin anti- αβ TCR monoclonal antibody αβ TCR Magnetic column Immuno-magnetic micro-bead attached to magnetic column eliminating the αβ T cells CliniMACs Plus Eluent of depletion process containing CD34+ cells, NK cells, and γδ T cells
22 CliniMACs cell separator system Immuno-magnetic microbead Biotin anti- αβ TCR monoclonal antibody Αβ TCR Magnetic column Immuno-magnetic microbead attaced to magnetic colum eliminating the αβ T cells CliniMACs Plus Eluent of depletion process containing CD34+ cells, NK cells, and γδ T cells
23 αβ T-cell/CD19 cell depleted haploidentical SCT n Graft Graft failure Relapse agvhd cgvhd NRM DFS/EFS OS Handgretinger (212) 25 PBSC 12% 13 36% 28% 16% N/A N/A Bertaina (214) 23 PBSC 17% N/A 13% % (18 mo) 9% 91% (2 yrs) N/A Balashov (215) 37 PBSC 27% N/A 22% 5% (15 mo) 3% N/A 97% (1 yr) γδ T cells & NK cells exert anti-leukemic effects (GVL but less likely GVHD) Decrease NRM but more GVHD Also use in non-malignant hematologic diseases Saad A and Lamb LS. Bone Marrow Transplant. 217 Sep;52(9):
24 Leukemic free survival Overall survival Cumulative incidence of relapse Cumulative incidence of NRM Evolution of TCD haploidentical HSCT Years Years Years Years ClinicMACs Technology Sestili S et al. Cancer. 218 Feb 22. doi: 1.2/cncr.3131
25 T cell Repleted Haploidentical Transplantation: Hopkins Protocol Cyclophosphamide (Cy) 14.5 mg/kg/day BMT Day Bone Marrow Infusion TBI G-CSF 2 cgy Mouse model data: Induced T cell tolerance Initial data comparing: Post-Cy Day +3 vs Day +3,+4 More cgvhd in Day +3 cohort MMF Tacrolimus Fludarabine 3 mg/m 2 /day Cy 5 mg/kg/day Day 3 or Days 3&4 Luznik L et al. Biol Blood Marrow Transplant. 28 Jun;14(6):641-5
26 Post-Transplant Cyclophosphamide (PTCy) T-cell activation T-cell proliferation Luznik L et al. Biol Blood Marrow Transplant. 28 Jun;14(6):641-5
27 Selective effect of cyclophosphamide High ALDH Lymphocytes show heterogeneous ALDH1 expression: Most T cells, esp. those proliferating, express low levels of ALDH1 and are sensitive to Cy Memory T cells, like other stem-like cells, express high levels and are resistant to Cy Low ALDH Low ALDH in alloreactive T cell High ALDH in Treg and naïve T cell
28 Cumulative incidence (%) Survival (%) Event Free Survival (%) Outcome Post-transplant cyclophosphamide 8 Relapse OS 6 4 Lymphoid (n=36) 2 Non-relapse mortality 5 15 Days after transplant 2 EFS 5 15 Days after transplant 2 Myeloid (n=31) 5 15 Days after transplant Very low non-relapse mortality but concerning high relapse rate High risk disease index patients population: Adjusted RDI No difference in relapse Luznik L et al. Biol Blood Marrow Transplant. 28 Jun;14(6):641-5
29 HLA haploidentical transplant with PTCY Myeloablative regimens decreased relapse but increased NRM No difference in overall survival Subsequent data on PBSC graft: No difference in outcome
30 Modified Hopkins Protocol Myeloablative regimens Thiotepa-Busulfan-Fludarabine or Fludarabine-TBI with bone marrow graft Prophylaxis with CSA (D-1) + MMF (D ) Post-transplant CTX (+3, +5) Treosulfan-Fludatabine with PBSC graft ATG + MMF + Rapamycin + CTX
31 T cell Repleted Haploidentical Transplantation: GIAC Protocol Ara-C 4 g/m 2 /d M-CCNU 25 mg/m 2 Cy 1.8 g/m 2 /d BM + GCSF stimulated T cell replete PBSC T cell tolerance, by polarization of T cells from Th 1 to Th 2 phenotype, regulatory T cell/th 17 balance toward regulatory T cells Busulfan 3.2 mkd Anti-thymoglb 2.5 mg/kg/day Methotrexate MMF CSA Huang XJ et al. Bone Marrow Transplant. 26 Aug;38(4):291-7
32 Effects of G-CSF on Bone Marrow in Healthy Donors Induce immune cells alteration T cell polarization, from Th1 to Th2, Induce T cell hyporesponsive- ness Downregulation of adhesion molecule expression HuangXJ, et al. Clin Transplant 211: 25: 13 23
33 # Patients NMA/ MA BM/PB/ Both Engraftment (%) agvhd II-IV (%) cgvhd (%) 1 yr TRM (%) DFS (%) Relapse (%) Huang 26 Huang 29 Luo 214 Fu 214 Gao 214 Di Bartoloneo /167 // (2y) (2y) 25 /25 // (3y) (3y) 99 /99 /99/ (3y) 14 (5y) 115 /115 // /178 // (2y) /16 8// (5y) 28 (5y) Peccatori /121 /121/ (3y) 48 (3y) Lee / /83/ (~2y) - Montoro J et al. Leuk Lymphoma. 216 Aug;57(8):
34 Comparison between haploidentical SCT approach Clinical outcome T cell depletion GIAC protocol PTCy Engraftment Acute GVHD Chronic GVHD Infection/Deaths from infection Nonrelapse mortality Relapse Kanakry CG et al. Nat Rev Clin Oncol. 216 Jan;13(1):1-24
35 Donor selection in haploidentical SCT
36 NK cell effect on anti-leukemic effect: Complex Handgretinger R, Lang P, André MC, Blood. 216 Jun 3;127(26):3341-9
37 Survival Survival NK alloreactive effect on haploidentical SCT Any Remission Chemoresistant relapse NK alloreactive.8.6 Less relapse Less GvHD Better survival.4 P=.2.4 NK alloreactive.2. Non-NK alloreactive.2. P=.4 Non-NK alloreactive Years Years Ruggeri L et al. Blood. 27 Jul 1;11(1):433-4
38 NK cell KIR phenotype in haploidentical HSCT Handgretinger R, Lang P, André MC, Blood. 216 Jun 3;127(26):3341-9
39 NK cell KIR phenotype in haploidentical HSCT Haplotype B associated with more activatory receptor Handgretinger R, Lang P, André MC, Blood. 216 Jun 3;127(26):3341-9
40 Probability Probability Probability Probability KIR B content score in haploidentical SCT Cumulative incidence of relapse KIR haplotype A KIR haplotype B P= Years Event Free Survival KIR haplotype A KIR haplotype B P= Years Score Score 1, 2 Score 3, 4 P= Years Score Score 1, 2 Score 3, 4 P= Years Oevermann L et al. Blood. 214 Oct 23;124(17):2744-7
41 NK cell KIR phenotype in haploidentical SCT Babor F, Fischer JC, Uhrberg M. Front Immunol. 213 Feb 7;4:27
42 Rate % Maternal Ag Effect in transplantation: Complex & Inconsistence Mother IMA/NIMA (A2,B55,DR9/A33,B44,DR12) Patient IMA/IPA (A2,B55,DR9/A11,B35,DR4) Father IPA/NIPA (A11,B35,DR4/A24,B52,DR15) NIMA NIPA Mother Father NIMA mismatched sibling lower risk of relapse Siblings Type HLA compatibility Donor eligibility IMA/IPA NIMA/IPA IMA/NIPA NIMA/NIPA HLA-identical NIMA-mismatched NIPA-mismatched HLA-mismatched Suitable Unsuitable Days van Rood JJ et al. Blood. 22 Mar 1;99(5):1572-7
43 NIMA Effect on haploidentical transplantation Parents Haploidentical Siblings Mother NIMA/IMA a b Patient IMA/IPA b d Sib#1 NIMA/IPA a d Mismatched for maternal antigens (NIMA) Father NIPA/IPA c d *Exposure to IPA during pregnancy/delivery Sib#2 NIPA/IMA c b Mismatched for paternal antigens (NIPA) van Rood JJ et al. Blood. 22 Mar 1;99(5):1572-7
44 Relapse mortality Event Free Survival TRM TCD Haploidentical transplant: Donor effects Father donor Mother donor.6 Mother donor.1 P= Father donor.2. Father donor P< Years Mother donor P= Stern M et al. Blood. 28 Oct 1;112(7):299-5
45 agvhd gr 2-4 OS NRM OS TCR Haploidentical transplant: Donor effects P=.4 Donor < 3 yr Donor > 3 yr N=971 N= Days after HSCT P<.1 Donor < 3 yr Donor > 3 yr N=961 N= Days after HSCT P=.5 Male donor Female donor N=524 N= Days after HSCT P=.7 Male donor Female donor N=518 N= Days after HSCT P=.1 Paternal donor Maternal donor N=31 N= Days after HSCT Days after HSCT N=31 P=.1 Paternal donor Maternal donor N= Days after HSCT Donor < 3 yr Donor > 3 yr Male donor Female donor P=.4 N=239 N=971 P=.1 N=686 N= Days after HSCT P=.7 N=412 N=31 Paternal donors Maternal donors 2345 Days after HSCT Wang Yu et al. Blood. 214 Aug 7;124(6):843-5
46 Cumulative incidence of relapse NRM Overall Survival TCR Haploidentical transplant: Selecting donor Child Sibling Parent 3 yr CIR 56% vs 33% vs 28% Years since transplant Child Sibling Parent 3 yr CIR 22% vs 15% vs 12% Years since transplant Child Sibling Parent 3 yr OS 65% vs 58% vs 4% P=.19 Child vs Parent P =.82 Sibling vs Parent Years since transplant Solomon SR et al. Biol Blood Marrow Transplant. 218 Jan 31. pii: S (18)328-4
47 Selection of Haplo-Donor: Summary 1. Male, younger donor preferred Negative ABO No or minor incompatible donor 2. Children>sibling> father>mother Haplo-donor Check DSA 3. NIMA-mismatch Desensitization Positive 4. KIR mismatched Choose DSA negative donor if possible 5. Matched CMV IgG serology
48 Certain limitation of haplo SCT
49 Immunologic basis of graft failure CTL NK DSAY TGF-β + IL-2 KGF HLA-directed DSA occurred in 14.5% of all patients and 42% of women undergoing haplotransplant evaluation Yoshihara S et al. Bone Marrow Transplant. 212 Apr;47(4):58-15 Masouridi-Levrat S et al. Front Immunol. 216 Sep 16;7:362
50 Cumulative incidence of engraftment Immunologic basis of graft failure CTL NK 1. DSA negative DSAY TGF-β.8.6 DSA positive IL-2 KGF.2 P=.26 HLA-directed DSA occurred in 14.5% of all patients and 42% of women undergoing haplotransplant evaluation Days after HSCT Yoshihara S et al. Bone Marrow Transplant. 212 Apr;47(4):58-15 Masouridi-Levrat S et al. Front Immunol. 216 Sep 16;7:362
51 Donor specific antibody in haploidentical SCT Study Patients # Conditioning Anti-HLA % DSA % Graft failure w or wo DSA Yoshihara 212 Ciurea 29 Chang 215 Ciurea RIC vs 3% 24 RIC ND 21 6% vs 5% 345 MAC % vs 3.2% 122 Non specified ND vs 4% Morin-Zorman S et al. Front Immunol. 216 Aug 12;7:37.
52 DSA desensitization methods N Anti-HLA test Desensitization method MFI post treatment Graft outcome Barge 1989 Braun 2 Ciurea 29 Yoshihara 212 Ciurea 215 Leffell CDC Plasmapheresis NA Graft failure 1 FCXM Staphylococcal Protein A immunoadsorption Negative XM Engrafted 4 Luminex MFI > 5 Plasmapheresis + rituximab One neg, 1 low titer, 2 high titer Pt w DSA neg and low titer engrafted 5 Luminex MFI > 5 Plasmapheresis + Rituximab (n=2), platelet transfusion (n=2), Bortezomib + Dex (n=1) 12 Luminex MFI > 5 Plasmapheresis + Rituximab + IVIG (n=5), PE + Rituximab + IVIG + donor buffy coat (n=7) 13 Luminex MFI > Plasmapheresis + IVIG + Tacrolimus 1 had temporary DSA reduction and 1 had significant DSA reduction after plasmapheresis, 2 had significant reduction post platelet transfusion, 1 had moderate DSA reduction after Bortezomib-dex No significant change of MFI before transplant, all patients cleared DSA after transplant Mean reduction of DSA post Rx 64.4% All 5 pt. engrafted 5 patients with C1q positive post treatment had GF while patients who became C1q negative engrafted All patients engrafted by D+4 Ciurea SO et al. Bone Marrow Transplant. 218 Jan 15. doi: 1.138/s
53 Infection in Haploidentical SCT Early experience High rate of graft failure in TCD haploidentical transplant High rate of infection and transplant related mortality Later experience: Improved engraftment rate: Neutrophil engraftment up to 21 days so similar bacterial infection to MSD T cell recovery is a prognostic determinant of infectious outcome Lower T cell and dendritic cell recovery compared to MSD TCD differ from TCR Atilla E et al. Infection. 217 Aug;45(4): Chang YJ et al. J Clin Immunol. 212 Apr;32(2):268-8
54 Immune reconstitution after haploidentical SCT 5 CD4+ T cells Day 3 Day 9 Day 18 HLA-Matched Haploidentical CD8+ T cell CD4+ T cell CD8+ T cells D3 D9 D18 TCD D3 D9 D18 TCR 5 Day 3 Day 9 Day 18 HLA-Matched Haploidentical B cells Day 3 Day 9 Day NK cell D3 D9 D B cell D3 D9 D18 HLA-Matched Haploidentical Atilla E et al. Infection. 217 Aug;45(4): Chang YJ et al. J Clin Immunol. 212 Apr;32(2):268-8
55 Comparison infection rate in haploidentical SCT Haploidentical MSD MUD UCB Transplant related mortality 18% 24% 33% 35% CD4+ T cell/μl at day Cumulative incidence of CMV reactivation Infection incidence at day +: - Bacterial - Fungal 74% 58% 6% 68% 25% 11% 23% 4% 36% 14% CMV was the most frequent viral infection in haploidentical SCT 39% 14% Rate of fatal infections 11% 4% 14% 17% Raiola AM et al. Biol Blood Marrow Transplant. 214 Oct;2(1):1573-9
56 Viral infection in haploidentical SCT Herpesviruses - HSV - CMV - HHV-6 - EBV - VZV - Patients infected > 1 herpesvirus Other viruses - Adenoviruses - Polyomavirus (JC/BK) - RSV - Influenza A virus - Patients infected > 1 viruses All patients (n=55) TCD (n=28) n (%) 8 (29.6) 12 (42.9) 23 (82.1) 19 (71.4) 2 (7.1) 26 (92.9) 5 (17.9) 11 (39.3) 1 (3.6) 2 (7.1) 27 (92.9) TCR/PTCY (n=27) n (%) 2 (7.4) 4 (14.8) 21 (77.8) 5 (18.6) () 6 (22.2) 4 (14.8) 13 (48.1) () 1 (3.7) 19 (7.3) Tischer J et al. Ann Hematol. 215 Oct;94(1):
57 Haploidentical SCT vs other SCT approaches
58 Survival (%) Survival (%) cgvhd Cumulative incidence (%) cgvhd Cumulative incidence (%) Cumulative incidence (%) Cumulative incidence (%) agvhd Cumulative incidence (%) agvhd Cumulative incidence (%) BMT CTN 63 vs BMT CTN 64: Parallel Study 8 6 Double UCB Relapse NRM 8 6 Haplo-BM Relapse NRM 8 6 Double UCB Grade II-IV Grade III-IV 8 6 Haplo-BM Grade II-IV Grade III-IV Days after transplantation Days after transplantation Days after transplantation Days after transplantation Overall Survival Event Free Survival 2 Overall Survival Event Free Survival Months after transplantation Months after transplantation Days after transplantation Days after transplantation Brunstein CG et al. Blood. 211 Jul 14;118(2):282-8
59 Haploidentical BMT vs Umbilical Cord Blood SCT Awaiting data from BMT CTN 111: Estimated sample size n = 4 Patient 18 and 7 yrs. Acute leukemia or lymphoma Adequate organ function Performance score 7 Available both 1) 4-6/6 HLA-matched UCB units 2) 4-6/8 HLA matched related donor Double UCB Randomization Stratified by Transplant Center Haplo-BM Day -6, -5 Fludarabine 3 mg/m 2 IV over 3-6 minutes, then Cyclophosphamide 14.5 mg/kg IV over 1-2 hours * Day -4-2 Fludarabine 3 mg/m 2 IV over 3-6 minutes Day -1 TBI 2 cgy Day Non-T-cell depleted bone marrow Days 3, 4 Cyclophopshamide 5 mg/kg IV Mesna 4 mg/kg IV* Day 5 Begin tacrolimus (or cyclosporine), mycophenolate mofetil, and G- CSF Day -6 Day -5-2 Day -3 Day -1 Day Day 1 Haploidentical HSCT PREPARATIVE REGIMEN ducb HSCT PREPARATIVE REGIMEN Fludarabine 4 mg/m 2 IV over 3-6 minutes, then Cyclophosphamide 5 mg/kg IV over 2 hours Fludarabine 4 mg/m 2 IV over 3-6 minutes Begin cyclosporine (or tacrolimus) and MMF TBI 2 cgy UCB Transplant Begin G-CSF
60 Haploidentical SCT vs Matched unrelated donor MA NMA % % % 2 14% NRM Relapse Overall Survival URD Haplo % Years Years Years 23% 9% % URD Haplo 44% 39% 58% 42% % % 5% 45% 46% 44% URD Haplo Years Years Years Ciurea SO et al. Blood. 215 Aug 2;126(8):133-4
61 Adjusted prob % Adjusted prob % Adjusted prob % Haploidentical Transplant vs Matched Sibling Haplo Sib 61% Matched Sib 61% P= Years Patient age, years: comparable survival after transplants from an HLA matched sibling and a haploidentical sibling Patient age, years: better survival after transplants from an HLA-matched sibling compared with offspring Robinson TM et al. Blood Adv. 218 Jun 12;2(11): Matched Sib 51% Offspring 44% 1 2 Years OS P= Haplo sib 15% Matched sib 13% 1 Years P=.52 P<.1 Matched sib 52% Haplo sib 42% 1 Years Offspring 21% 2 Matched Sib 17% Years cgvhd P=.25 P<.1 NRM Matched Sib 46% Offspring 28% 1 2 Years
62 Cumulative percentage Comparison of SCT in acute myeloid leukemia 75 MSD MUD1/1 Haplo 5 25 MUD 9/1 CB Cox LR P<.1 Overall Survival Months Fabricius WA. Adv Hematol. 216;216:
63 Cumulative percentage Comparison of SCT in acute myeloid leukemia 75 MSD Haplo MUD1/ MUD 9/1 CB Cox LR P<.1 Overall Survival Months Fabricius WA. Adv Hematol. 216;216:
64 Trend in haploidentical vs other allogeneic SCT HAPLO Mism unrelated Other Relative Single Cord Double Cord Related Cord Pasquini MC, Zhu X. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 215
65 Conclusions Haploidentical transplantation is an attractive transplant regimen based on the ready availability of donors Based on mostly retrospective data, current evidence suggests similar OS and possibly superior GVHD rate as compared with MUD or MRD transplantation Better understanding in immunology will result in better donor selection strategy to improve transplant outcome Active research in combining haploidentical transplant approach Extended indication of haploidentical transplant to all hematologic conditions
66 THANK YOU FOR YOUR ATTENTION Any Questions?
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