HLA-DPB1 mismatch reduce relapse and improve survival in T-cell replete unrelated donor allogeneic stem cell transplantation

Grønvold, B.; Ali, Maryan; Remberger, Mats; Mattsson, Jonas; Egeland, Torstein; Lundin, Katrin U.; Myhre, Anne Grethe; Abrahamsen, Ingerid Weum; Heldal, Dag; Dybedal, Ingunn; Tjønnfjord, Geir E.; Fløisand, Yngvar; Gedde‐Dahl, Tobias

doi:10.1038/s41409-020-0827-3

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“…Although HLA-DQ mismatch is linked through strong linkage disequilibrium with HLA-DR, its tolerability is higher (19,20). Concerning HLA-DP, a non-permissive mismatch has been reported to induce adverse effects, depending on the overall number of mismatches and its association with other HLA mismatches (37)(38)(39). We hypothesized that a higher class II HED could be associated with an increase in the allo-antigens presented by the host's antigen-presenting cells.…”

Section: Discussionmentioning

confidence: 97%

Class I/Class II HLA Evolutionary Divergence Ratio Is an Independent Marker Associated With Disease-Free and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

et al. 2022

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Class I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p<0.001), independently of HLA matching and other HCT parameters. No significant association was found between the ratio and graft-versus-host disease (GvHD) nor with neutrophil and platelet recovery. A high class I HED was associated with a tendency for an increase in NK, CD8 T-cell, and B cell recovery at 12 months. These results introduce HED as an original and independent prognosis marker reflecting immunopeptidome diversity and alloreactivity after HCT.

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