Revised HLA-DP TCE-Core Permissiveness Model Better Defines Relapse Risk and Survival following Haploidentical...

Area of Science:

• Immunogenetics
• Hematopoietic Stem Cell Transplantation
• HLA Matching

Background:

• The HLA-DPB1 nonpermissive mismatch (NPMM) using the TCE-3 model is linked to better outcomes in haploidentical donor transplantation (HIDT) with post-transplantation cyclophosphamide (PTCy).
• A revised model, TCE-Core, refines the classification of TCE-3 'group 3' alleles into 'core' (C) and 'noncore' (NC), reclassifying some previously permissive mismatches as C-NPMM.

Purpose of the Study:

• To evaluate the impact of HLA-DPB1 C-NPMM, as defined by the TCE-Core algorithm, on HIDT outcomes.
• To assess the influence of the mismatch's directional vector (graft-versus-host vs. host-versus-graft) on transplantation results.
• To compare the discriminatory power of the TCE-Core model against the conventional TCE-3 algorithm for predicting survival.

Main Methods:

• Analysis of 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome transplanted between 2005 and 2021.
• Reclassification of 136 TCE-3 permissive mismatches using the TCE-Core algorithm to identify C-NPMMs.
• Comparison of overall survival (OS) and disease-free survival (DFS) between permissive and nonpermissive groups, considering mismatch directionality.

Main Results:

• The TCE-Core model identified a higher proportion of nonpermissive transplants (38% vs. 23%) and showed a greater survival benefit compared to TCE-3.
• TCE-Core-defined nonpermissive HLA-DP mismatch was associated with superior 5-year OS (66% vs. 47%) and DFS (60% vs. 43%).
• Multivariable analysis confirmed that a nonpermissive TCE-Core mismatch significantly improved OS and DFS, primarily by reducing relapse risk (HR, .63; P = .049), without adversely affecting GVHD or NRM.

Conclusions:

• The TCE-Core algorithm provides a more accurate assessment of HLA-DP mismatch status, significantly predicting improved survival in PTCy-based HIDT.
• The reduction in relapse risk associated with TCE-Core-defined nonpermissive mismatches enhances patient outcomes without increasing mortality or GVHD.
• TCE-Core serves as a superior donor selection tool, better discriminating HIDT outcomes and potentially expanding the donor pool.