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Use of the HLA-B leader to optimize cord blood transplantation

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 unrelated single-unit cord blood transplants p...

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Autores principales: Petersdorf, Effie W., Gooley, Ted, Volt, Fernanda, Kenzey, Chantal, Madrigal, Alejandro, McKallor, Caroline, Querol, Sergio, Rafii, Hanadi, Rocha, Vanderson, Tamouza, Ryad, Chabannon, Christian, Ruggeri, Annalisa, Gluckman, Eliane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634170/
https://www.ncbi.nlm.nih.gov/pubmed/33121238
http://dx.doi.org/10.3324/haematol.2020.264424
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author Petersdorf, Effie W.
Gooley, Ted
Volt, Fernanda
Kenzey, Chantal
Madrigal, Alejandro
McKallor, Caroline
Querol, Sergio
Rafii, Hanadi
Rocha, Vanderson
Tamouza, Ryad
Chabannon, Christian
Ruggeri, Annalisa
Gluckman, Eliane
author_facet Petersdorf, Effie W.
Gooley, Ted
Volt, Fernanda
Kenzey, Chantal
Madrigal, Alejandro
McKallor, Caroline
Querol, Sergio
Rafii, Hanadi
Rocha, Vanderson
Tamouza, Ryad
Chabannon, Christian
Ruggeri, Annalisa
Gluckman, Eliane
author_sort Petersdorf, Effie W.
collection PubMed
description 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 unrelated 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 HLAA and HLA-A and -DRB1 matched. The leader (methionine [M] or threonine [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 determined. The risks of graft-versus-host disease, relapse, non-relapse mortality 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 Mleader 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 selection of units that consider the leader.
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spelling pubmed-86341702021-12-17 Use of the HLA-B leader to optimize cord blood transplantation Petersdorf, Effie W. Gooley, Ted Volt, Fernanda Kenzey, Chantal Madrigal, Alejandro McKallor, Caroline Querol, Sergio Rafii, Hanadi Rocha, Vanderson Tamouza, Ryad Chabannon, Christian Ruggeri, Annalisa Gluckman, Eliane Haematologica Article 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 unrelated 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 HLAA and HLA-A and -DRB1 matched. The leader (methionine [M] or threonine [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 determined. The risks of graft-versus-host disease, relapse, non-relapse mortality 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 Mleader 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 selection of units that consider the leader. Fondazione Ferrata Storti 2020-10-29 /pmc/articles/PMC8634170/ /pubmed/33121238 http://dx.doi.org/10.3324/haematol.2020.264424 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Petersdorf, Effie W.
Gooley, Ted
Volt, Fernanda
Kenzey, Chantal
Madrigal, Alejandro
McKallor, Caroline
Querol, Sergio
Rafii, Hanadi
Rocha, Vanderson
Tamouza, Ryad
Chabannon, Christian
Ruggeri, Annalisa
Gluckman, Eliane
Use of the HLA-B leader to optimize cord blood transplantation
title Use of the HLA-B leader to optimize cord blood transplantation
title_full Use of the HLA-B leader to optimize cord blood transplantation
title_fullStr Use of the HLA-B leader to optimize cord blood transplantation
title_full_unstemmed Use of the HLA-B leader to optimize cord blood transplantation
title_short Use of the HLA-B leader to optimize cord blood transplantation
title_sort use of the hla-b leader to optimize cord blood transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634170/
https://www.ncbi.nlm.nih.gov/pubmed/33121238
http://dx.doi.org/10.3324/haematol.2020.264424
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