Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation

Lee Ann Baxter-Lowe, Tao Wang, Michelle Kuxhausen, Stephen R. Spellman, Martin Maiers, Stephanie Lee, Jennifer Saultz, Esteban Arrieta-Bolaños, Shahinaz M. Gadalla, Yung Tsi Bolon, Brian C. Betts

Research output: Contribution to journalArticlepeer-review

Abstract

Background: When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated. Methods: High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain. The location and physicochemical properties of mismatched amino acids were used to assign scores for peptide binding, T-cell receptor docking, and HLA structure/function. The scores were tested using a cohort of 2319 patients with leukemia or myelodysplastic syndrome who received their first unrelated donor transplant using conventional graft-versus-host disease (GVHD) prophylaxis between 2000 and 2014. Donors were 7/8 HLA-matched with a single HLA Class I mismatch. Primary outcomes were overall survival and acute GVHD. Results: The scores did not significantly (p < 0.01) associate with transplant outcomes, although a Peptide Score = 0 (i.e., no differences in peptide binding; N = 146, 6.3%) appears to have lower transplant-related mortality (TRM) compared to higher scores (p = 0.019). HLA mismatches with Peptide Score = 0 were predominately HLA-C*03:03/03:04 (62%), previously reported to be a permissive mismatch, and a group of 28 other HLA mismatches (38%) that showed similar associations with TRM. Conclusions: This study suggests that HLA mismatches that do not alter peptide binding or orientation (Peptide Score = 0) could expand the number of permissive HLA mismatches. Further investigation is needed to confirm this observation and to explore alternative scoring systems for ranking HLA mismatched donors.

Original languageEnglish (US)
Article numbere15478
JournalClinical Transplantation
Volume38
Issue number11
DOIs
StatePublished - Nov 2024

Keywords

  • HLA mismatch
  • HSCT
  • scoring system
  • unrelated donors

ASJC Scopus subject areas

  • Transplantation

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