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High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation.


ABSTRACT: HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome. In this study, we determined the phased haplotypes of 291 patients using family members and segregation analysis. The sum of ranks of the haplotypes carried by patients was used as a surrogate predictor of a successful unrelated donor search. The putative impact of haplotypes was then analyzed in a cohort of 211 recipients transplanted with 10/10 matched unrelated donors. A logistic regression analysis showed a highly significant effect of the haplotypes in the outcome of a search, but we did not find any significant effect on overall survival, graft versus host disease or relapse/progression following HSCT. This study provides useful data for the optimization of unrelated bone marrow donor searches, but does not confirm previous reports that matching at the haplotype level has a clinical impact following HSCT. Due to the extreme polymorphism of HLA genes, further studies are warranted to better understand the many factors at play.

SUBMITTER: Buhler S 

PROVIDER: S-EPMC7198472 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation.

Buhler Stéphane S   Baldomero Helen H   Ferrari-Lacraz Sylvie S   Nunes José Manuel JM   Sanchez-Mazas Alicia A   Massouridi-Levrat Stravroula S   Heim Dominik D   Halter Jörg J   Nair Gayathri G   Chalandon Yves Y   Schanz Urs U   Güngör Tayfun T   Nicoloso Grazia G   Tiercy Jean-Marie JM   Passweg Jakob J   Villard Jean J  

Bone marrow transplantation 20190405 10


HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome. In this study, we determined the phased haplotypes of 291 patients using family members and segregation analysis. The sum of ranks of the haplotypes carried b  ...[more]

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