Faculty Collaboration Database

HLA-B leader and survivorship after HLA-mismatched unrelated donor transplantation. Blood 2020 Jul 16;136(3):362-369

Date

06/03/2020

Pubmed ID

32483623

Pubmed Central ID

PMC7365916

DOI

10.1182/blood.2020005743

Scopus ID

2-s2.0-85088276743 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Hematopoietic cell transplantation (HCT) from HLA-mismatched unrelated donors can cure life-threatening blood disorders, but its success is limited by graft-versus-host disease (GVHD). HLA-B leaders encode methionine (M) or threonine (T) at position 2 and give rise to TT, MT, or MM genotypes. The dimorphic HLA-B leader informs GVHD risk in HLA-B-mismatched HCT. If the leader influences outcome in other HLA-mismatched transplant settings, the success of HCT could be improved for future patients. We determined leader genotypes for 10 415 patients receiving a transplant between 1988 and 2016 from unrelated donors with one HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatch. Multivariate regression methods were used to evaluate risks associated with patient leader genotype according to the mismatched HLA locus and with HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatching according to patient leader genotype. The impact of the patient leader genotype on acute GVHD and mortality varied across different mismatched HLA loci. Nonrelapse mortality was higher among HLA-DQB1-mismatched MM patients compared with HLA-DQB1-mismatched TT patients (hazard ratio, 1.35; P = .01). Grades III to IV GVHD risk was higher among HLA-DRB1-mismatched MM or MT patients compared with HLA-DRB1-mismatched TT patients (odds ratio, 2.52 and 1.51, respectively). Patients tolerated a single HLA-DQB1 mismatch better than mismatches at other loci. Outcome after HLA-mismatched transplantation depends on the HLA-B leader dimorphism and the mismatched HLA locus. The patient's leader variant provides new information on the limits of HLA mismatching. The success of HLA-mismatched unrelated transplantation might be enhanced through the judicious selection of mismatched donors for a patient's leader genotype.

Author List

Petersdorf EW, Stevenson P, Bengtsson M, De Santis D, Dubois V, Gooley T, Horowitz M, Hsu K, Madrigal JA, Malkki M, McKallor C, Morishima Y, Oudshoorn M, Spellman SR, Villard J, Carrington M

Author

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Allografts
Child
Child, Preschool
Disease-Free Survival
Female
Graft vs Host Disease
HLA-B Antigens
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Middle Aged
Retrospective Studies
Survival Rate
Unrelated Donors