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Bone Marrow Transplantation
Use of the HLA-B leader to optimize cord blood transplantation
Effie W. Petersdorf,1,2 Ted Gooley,1 Fernanda Volt,3 Chantal Kenzey,3 Alejandro Madrigal,4 Caroline McKallor,1 Sergio Querol,5 Hanadi Rafii,3 Vanderson Rocha,3,6 Ryad Tamouza,3,7 Christian Chabannon,8,9 Annalisa Ruggeri3,9,10 and Eliane Gluckman3,11
1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 2Department of Medicine, University of Washington, Seattle, WA, USA; 3Eurocord, Hôpital Saint Louis APHP, Institut de Recherche de Saint-Louis (IRSL) EA3518, Université de Paris, Paris, France; 4University College London Cancer Institute, Royal Free Campus, London, UK; 5Cell Therapy Services, Catalan Blood and Tissue Bank, Barcelona, Spain, 6Hospital das Clínicas and LIM31, Faculty of Medicine University of São Paulo, Brazil; 7INSERM U955, CHU Henri Mondor, Créteil, France, 8Institut Paoli- Calmettes, INSERM CBT1409, Marseille, France; 9Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation, Leiden, the Netherlands; 10Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy and 11Monacord, International Observatory on Sickle Cell Disease, Centre Scientifique de Monaco, Monaco
ABSTRACT
Cord blood transplantation (CBT) can cure life-threatening blood disorders. The HLA-B leader affects the success of unrelated donor transplantation but its role in CBT is unknown. We tested the hypothesis that the HLA-B leader influences CBT outcomes in unre- lated single-unit cord blood transplants performed by Eurocord/European Blood and Marrow Transplant (EBMT) centers between 1990 and 2018 with data reported to Eurocord. Among 4,822 transplants, 2,178 had one HLA-B mismatch of which 1,013 were HLA- A and HLA-A and -DRB1 matched. The leader (methionine [M] or thre- onine [T]) was determined for each HLA-B allele in patients and units to define the genotype. Among single HLA-B-mismatched transplants, the patient/unit mismatched alleles were defined as leader-matched if they encoded the same leader, or leader-mismatched if they encoded different leaders; the leader encoded by the matched (shared) allele was deter- mined. The risks of graft-versus-host disease, relapse, non-relapse mortal- ity and overall mortality were estimated for various leader-defined groups using multi-variable regression models. Among the 1,013 HLA-A and -DRB1-matched transplants with one HLA-B mismatch, increasing numbers of cord blood unit M-leader alleles was associated with increased risk of relapse (hazard ratio [HR] for each increase in one M- leader allele 1.30, 95% Confidence Interval [CI]: 1.05-1.60, P=0.02). Furthermore, leader mismatching together with an M-leader of the shared HLA-B allele lowered non-relapse mortality (HR 0.44, 95% CI: 0.23-0.81; P=0.009) relative to leader matching and a shared T-leader allele. The HLA-B leader may inform relapse and non-relapse mortality risk after CBT. Future patients might benefit from the appropriate selec- tion of units that consider the leader.
Introduction
Cord blood transplantation (CBT) offers curative therapy for life-threatening blood disorders. Its distinct advantages are 2-fold. Similar to haploidentical donor transplantation, the less stringent level of histocompatibility required between the patient and the cord blood unit is an asset for patients of diverse ancestry who lack HLA-matched peripheral blood stem cell and marrow donors.1-11 Compared to other sources of allogeneic stem cells, a unique benefit of cord blood transplanta- tion is the avoidance of risks to the donor. The lower risk of severe acute and
Ferrata Storti Foundation
Haematologica 2021 Volume 106(12):3107-3114
Correspondence:
EFFIE W. PETERSDORF
epetersd@fredhutch.org
Received: June 23, 2020. Accepted: October 15, 2020. Pre-published: October 29, 2020.
https://doi.org/10.3324/haematol.2020.264424 ©2021 Ferrata Storti Foundation
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