Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation

Area of Science:

• Immunogenetics
• Transplantation immunology
• Hematology

Background:

• Hematopoietic stem cell transplantation (HSCT) relies on human leukocyte antigen (HLA) matching for optimal outcomes.
• Lack of universally accepted guidelines for ranking 7/8 HLA-matched unrelated donors poses challenges when HLA-matched donors are unavailable.
• A novel scoring system was investigated to rank HLA mismatches in unrelated donor HSCT.

Purpose of the Study:

• To investigate a novel scoring system for ranking single HLA Class I mismatches in 7/8 HLA-matched unrelated donor HSCT.
• To assess the association of this scoring system with overall survival and acute graft-versus-host disease (GVHD).

Main Methods:

• High-resolution HLA typing to identify amino acid mismatches in the HLA antigen-recognition domain.
• Scoring of mismatches based on physicochemical properties affecting peptide binding, T-cell receptor docking, and HLA structure/function.
• Analysis of a cohort of 2319 leukemia/myelodysplastic syndrome patients undergoing first unrelated donor HSCT.

Main Results:

• The novel scoring system did not significantly correlate with transplant outcomes (overall survival, acute GVHD).
• A Peptide Score of 0 (no peptide binding alteration) was associated with lower transplant-related mortality (TRM) (p=0.019).
• HLA mismatches with Peptide Score = 0 included HLA-C*03:03/03:04 and other specific mismatches, previously suggested as permissive.

Conclusions:

• HLA mismatches that do not alter peptide binding (Peptide Score = 0) may represent permissive mismatches, potentially expanding the donor pool.
• Further research is required to validate these findings and explore alternative scoring systems for HLA mismatched donor selection.