Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784608082425282560 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8634170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT petersdorfeffiew useofthehlableadertooptimizecordbloodtransplantation AT gooleyted useofthehlableadertooptimizecordbloodtransplantation AT voltfernanda useofthehlableadertooptimizecordbloodtransplantation AT kenzeychantal useofthehlableadertooptimizecordbloodtransplantation AT madrigalalejandro useofthehlableadertooptimizecordbloodtransplantation AT mckallorcaroline useofthehlableadertooptimizecordbloodtransplantation AT querolsergio useofthehlableadertooptimizecordbloodtransplantation AT rafiihanadi useofthehlableadertooptimizecordbloodtransplantation AT rochavanderson useofthehlableadertooptimizecordbloodtransplantation AT tamouzaryad useofthehlableadertooptimizecordbloodtransplantation AT chabannonchristian useofthehlableadertooptimizecordbloodtransplantation AT ruggeriannalisa useofthehlableadertooptimizecordbloodtransplantation AT gluckmaneliane useofthehlableadertooptimizecordbloodtransplantation |