Extended HLA haplotypes and transplant survival

Area of Science:

• Immunogenetics
• Transplantation immunology
• Genomic medicine

Background:

• The role of extended human leukocyte antigen (HLA) class I, III, and II haplotypes in hematopoietic-cell transplantation (HCT) success is not fully understood.
• Functional variation within the HLA class III region is crucial but often overlooked in HCT donor selection.

Purpose of the Study:

• To investigate the impact of extended HLA haplotypes, including class III single-nucleotide polymorphisms (SNPs), on HCT outcomes.
• To identify specific HLA class III SNPs that predict mortality and relapse after HCT.

Main Methods:

• Multivariable regression analysis of 26 candidate class III SNPs in 1,436 patients and their haploidentical related donors.
• Haplotype analysis incorporating class I, class II loci, and the identified class III SNP (rs915654).
• Validation in an independent cohort of 1,141 haploidentical transplants.

Main Results:

• A specific class III SNP, rs915654, was significantly associated with reduced mortality and relapse.
• Incorporating rs915654 into existing HLA models improved their predictive power for relapse and mortality.
• The number of favorable patient and donor markers correlated inversely with mortality and relapse risks, including non-relapse mortality.

Conclusions:

• Extended HLA class I-III-II haplotypes significantly influence HCT success.
• The identified class III SNP (rs915654) provides valuable prognostic information.
• Optimizing haploidentical donor selection using comprehensive HLA haplotype data can improve transplant outcomes.