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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 54; no. 10; pp. 1701 - 1709
• Main Authors: Buhler, Stéphane, Baldomero, Helen, Ferrari-Lacraz, Sylvie, Nunes, José Manuel, Sanchez-Mazas, Alicia, Massouridi-Levrat, Stravroula, Heim, Dominik, Halter, Jörg, Nair, Gayathri, Chalandon, Yves, Schanz, Urs, Güngör, Tayfun, Nicoloso, Grazia, Tiercy, Jean-Marie, Passweg, Jakob, Villard, Jean
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2019; Nature Publishing Group
• Subjects: 45/22; 45/77; 631/250/1854; 631/250/1904; Bone marrow; Bone marrow transplantation; Cell Biology; Gene polymorphism; Genetic polymorphisms; Graft-versus-host reaction; Haplotypes; Hematology; Hematopoietic stem cells; High resolution; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; Internal Medicine; Matching; Medicine; Medicine & Public Health; Optimization; Polymorphism; Public Health; Regression analysis; Searching; Stem cell transplantation; Stem Cells; Tissue typing; Transplantation
• DOI: 10.1038/s41409-019-0520-6
• ISSN: 0268-3369

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.