Significance of Degree of HLA Disparity Using T-cell Replete Peripheral Blood Stem Cells From Haploidentical Donors With Posttransplantation Cyclophosphamide in AML in First Complete Hematologic Remission: A Study of the Acute Leukemia Working Party of the EBMT

Author:

Kharfan-Dabaja Mohamed A.1,Labopin Myriam23,Ayala Ernesto1,Bazarbachi Ali4,Blaise Didier5,Vydra Jan6,Bramanti Stefania7,Itälä-Remes Maija8,Schmid Christoph9,Busca Alessandro10,Forcade Edouard11,Rabitsch Werner12,Zecca Marco13,Kröger Nicolaus14,Bulabois Claude-Eric15,Grillo Giovanni16,Rambaldi Alessandro17,Fanin Renato18,Zallio Francesco19,Di Renzo Nicola20,Koc Yener21,Novis Yana22,McDonald Andrew23,Herrera Arroyo Concepcion24,Sanz Jaime25,Nagler Arnon26,Ciceri Fabio27,Mohty Mohamad23

Affiliation:

1. Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA

2. Department of Hematology, Hôpital Saint Antoine, Sorbonne University and INSERM UMRs 938, Paris, France

3. Acute Leukemia Working Party of EBMT, Paris, France

4. Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Lebanon

5. Programme de Transplantation and Therapie Cellulaire, Department of Hematology, Management Sport Cancer (MSC) Lab, Aix Marseille University, Institut Paoli Calmettes, Marseille, France

6. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

7. IRCCS Istituto Clinico Humanitas, Rozzano, Milano, Italy

8. Turku University Hospital, TD7 (Stem Cell Transplant Unit), Turku, Finland

9. Augsburg University Hospital and Medical Faculty, Augsburg, Germany

10. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino, Italy

11. Service d’Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, France

12. Medizinische Universitaet Wien, Klinik fuer Innere Medizin I Knochenmarktransplantation, Vienna, Austria

13. Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

14. University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany

15. CHU Grenoble Alpes - Université Grenoble Alpes, Service d`Hématologie, France

16. ASST Grande Ospedale Metropolitano Niguarda, Hematology Department, Milano, Italy

17. Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

18. Azienda Ospedaliero Universitaria di Udine, Division of Hematology, Italy

19. H SS. Antonio e Biagio, Haematology Department, Alessandria, Italy

20. Unita Operativa di Ematologia e Trapianto di cellule staminali, Lecce, Italy

21. Medicana International Hospital Istanbul, Bone Marrow Transplant Unit, Istanbul, Turkey

22. Hospital Sirio-Libanes, Hematology Bone Marrow Transplant Unit, Sao_Paulo, Brazil

23. Alberts Cellular Therapy, Netcare Pretoria East Hospital, Pretoria, South Africa

24. Reina Sofia University Hospital, IMIBIC, University of Cordoba, Spain

25. Hematology Department, Hospital Universitari i Politècnic La Fe, Avinguda Fernando Abril Martorell, Valencia, Spain

26. Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel

27. Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy

Abstract

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2–3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2–3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2–3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2–4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2–3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

Publisher

Wiley

Subject

Hematology

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