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3910 Significance of Degree of HLA Disparity When Using Haploidentical Donors with T-Replete PBSC and Post-Transplantation Cyclophosphamide (PTCy) in Acute Myeloid Leukemia (AML) in First Complete Hematologic Remission (CR1)

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Biological, AML, Diseases, Therapies, Myeloid Malignancies, Transplantation
Monday, December 13, 2021, 6:00 PM-8:00 PM

Mohamed A. Kharfan-Dabaja, MD, MBA1, Myriam Labopin2*, Ernesto Ayala, MD3, Ali Bazarbachi, MD, PhD4, Didier Blaise5, Yener Koc, MD6, Jan Vydra, MD7*, Alessandro Busca, MD8*, Luca Castagna9*, Yana Novis, MD10*, Andrew McDonald, MD11*, Claude-Eric Bulabois, MD12*, Christoph Schmid, MD13*, Concepcion Herrera Arroyo, MD14*, Edouard Forcade, MD, PhD15, Fabio Ciceri, MD16*, Jaime Sanz, MD17*, Arnon Nagler, M.D.18 and Mohamad Mohty, MD, PhD2,19

1Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL
2Hôpital St Antoine, Sorbonne University, INSERM UMRs 938, Paris, France
3Division of Hematology-Oncology and Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL
4Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Dept. of Medicine, Beirut, Lebanon
5Programme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France
6Bone Marrow Transplant Unit, Medicana International Hospital Istanbul, Istanbul, Turkey
7Institute of Hematology and Blood Transfusion, Prague, Czech Republic
8Department of Oncology and Hematology, SSD Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
9Department of Oncology and Hematology, Transplantation Unit, Palermo, Italy, Italy
10Hematology Bone Marrow Transplant Unit, Hospital Sírio Libanês, São Paulo, Brazil
11Netcare Pretoria East Hospital, Pretoria, South Africa
12Service d'Hematologie, CHU Grenoble Alpes-Universite Grenoble Alpes, Grenoble, France
13Augsburg University Hospital, Augsburg, Germany
14Hospital Reina Sofia, Cordoba, Spain
15Service d’hematologie et thérapie Cellulaire, CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France
16Haematology and BMT, Ospedale San Raffaele s.r.l., Milano, Italy
17Hematology Department, Hospital Universitari I politècnic La Fe, Valencia, Spain
18Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
19Acute Leukemia Working Party of EBMT, Paris, France

Background: Haploidentical allogeneic hematopoietic cell transplantation (haplo) has expanded applicability of the procedure to patients for whom a suitable HLA compatible donor was not available in the past. A small multicenter retrospective study of 185 patients with hematologic malignancies who received a nonmyeloablative preparative regimen followed by infusion of bone marrow (BM) hematopoietic cells from haploidentical donors showed no significant association between the number of HLA mismatches (HLA-A, -B, -C, and -DRB1 combined) and risk of acute grade 2-4 graft-versus-host disease (GVHD) (hazard ratio [HR]=0.89; P=0.68 for 3-4 mismatches vs fewer antigen mismatches). This haploidentical transplant platform has certainly evolved. Nowadays, G-CSF mobilized peripheral blood stem cells (PBSC) are commonly used owing to its increased convenience vis-à-vis performing a BM harvest.

Study population: Here, we evaluate post transplant outcomes when using haploidentical donors with T-replete PBSC and PTCy in AML in CR1. A total of 494 patients (4/8 HLA mismatch (group 1)=360, 2-3/8 HLA mismatch (group 2)=134) underwent the procedure at an EBMT participating center. The primary endpoints were cumulative incidences of grade 2-4 acute GVHD and chronic (all grades) GVHD. Secondary endpoints included cumulative incidence of relapse (RI), non-relapse mortality (NRM), leukemia-free (LFS) and overall survival (OS) and GVHD-free relapse-free survival (GRFS).

Results: Group 1 and group 2 were not statistically different in regards to median age at allografting (54.1 vs. 56.1 years, p=0.51), median year of haplo transplantation (2018 vs. 2018, p=0.36), incidence of de novo AML (86.4% vs. 88.1%, p=0.63), Karnofsky equal or more than 90 (77.5% vs. 79.1%, p=0.70), and use of myeloablative conditioning (MAC) (44.7% vs. 48.5%, p=0.45). Patients in group 1 had a longer time from diagnosis to haplo-transplantation (5.3 vs. 4.9 months, p=0.03). In multivariate analysis, group 1 and group 2 did not differ in cumulative incidence of grade 2-4 acute GVHD (Hazard ratio (HR)=0.89 (95%CI=0.62-1.26), p=0.51) but group 1 had a significantly higher incidence of chronic (all grades) GVHD (HR=1.49 (95%CI=1.02-2.16), p=0.04). There was no difference in RI (HR=0.73 (95%CI=0.47-1.14), p=0.17), NRM (HR=1.25 (95%CI=0.78-2.02), p=0.36), LFS (HR=0.95 (95%CI=0.69-1.31), p=0.76), OS (HR=1.09 (95%CI=0.76-1.55), p=0.64) and GRFS (HR=1.07 (95%CI=0.81-1.42), p=0.64) between the groups. Presence of adverse cytogenetics was independently associated with higher RI (HR=1.90 (95%CI=1.20-2.99), p=0.006), inferior LFS (HR=1.59 (95%CI=1.15-2.19), p=0.005), inferior OS (HR=1.48 (95%CI=1.05-2.08), p=0.03), and worse GRFS (HR=1.54 (95%CI=1.17-2.04), p=0.002).

Conclusion: Results show that patients undergoing haplo-transplantation with 4/8 (vs. 2-3/8) HLA mismatches have a higher incidence of chronic GVHD (all grades) without adversely affecting acute grade 2-4 GVHD, RI, LFS, OS and GRFS.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Blaise: Jazz Pharmaceuticals: Honoraria. McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Forcade: Novartis: Other: travel grant. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Mohty: Takeda: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Honoraria.

*signifies non-member of ASH