HLA Haplotypes and Relapse After Hematopoietic Cell Transplantation

Area of Science:

• Immunogenetics
• Transplantation immunology

Background:

• Recurrent blood malignancy is a primary cause of hematopoietic cell transplant (HCT) failure.
• Human leukocyte antigen (HLA) class II molecules are crucial for anti-tumor responses, but the role of their haplotypes in HCT is not well understood.

Purpose of the Study:

• To investigate the clinical significance of individual HLA class II molecules and haplotypes in related haploidentical HCT.
• To determine if HLA class II haplotypes impact transplant outcomes, specifically relapse and mortality.

Main Methods:

• Analysis of HLA-DR, -DQ, -DM, and -DO allele variation in 1,629 related haploidentical transplants.
• Correlation of specific HLA variations and haplotypes with patient and donor factors and clinical outcomes.

Main Results:

• Patient and donor variations in HLA-DRβ residue 86, HLA-DQ heterodimers (G1/G2), and donor HLA-DM molecules significantly correlated with transplant outcomes.
• Specific HLA-DRβ-86 genotypes (GlyGly/GlyVal) and HLA-DQ (G1G2) mismatches were associated with lower relapse risks.
• Donor HLA-DMα residue 184 (ArgHis) was linked to a higher relapse risk compared to ArgArg.
• Significant differences in relapse and mortality risks were observed across various HLA-DR-DQ-DM haplotypes.

Conclusions:

• HLA class II haplotypes may function as critical components of the transplantation barrier.
• Incorporating HLA class II haplotype matching into patient and donor selection could enhance HCT success rates.