Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) Are Associated with Poorer Outcome after Single Mismatch Unrelated Donor Stem Cell Transplantation: A Study of the Cooperative Transplant Study Group (KTS) of the German Group for Bone Marrow and Stem Cell Transplantation (DAG-KBT)

TY - JOUR

T1 - Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) Are Associated with Poorer Outcome after Single Mismatch Unrelated Donor Stem Cell Transplantation: A Study of the Cooperative Transplant Study Group (KTS) of the German Group for Bone Marrow and Stem Cell Transplantation (DAG-KBT)

AU - Ayuk, Francis

AU - Bornhäuser, Martin

AU - Stelljes, Matthias

AU - Zabelina, Tatjana

AU - Wagner, Eva-Maria

AU - Schmid, Christoph

AU - Christopeit, Maximilian

AU - Guellstorf, Martina

AU - Kröger, Nicolaus

AU - Bethge, Wolfgang

N1 - Copyright © 2019 by S. Karger AG, Basel.

PY - 2019/10

Y1 - 2019/10

N2 - There is no established standard for selection of mismatched unrelated donors. Indirect recognition of HLA mismatches can be predicted using the model of "Predicted Indirectly ReCognizable HLA Epitopes" (PIRCHE). We performed a multicenter retrospective study evaluating the impact PIRCHE on outcome after allogeneic stem cell transplantation (allo-HSCT) from single mismatched (HLA 9/10 matched) unrelated donors. The study cohort included 424 adult recipients of HLA 9/10 matched unrelated donor transplants (9/10 MUD), treated for AML or MDS at 6 transplant centers across Germany. Detection of PIRCHE was associated with lower overall survival (OS) (47 vs. 57%, p = 0.04), higher non-relapse mortality (NRM) (32 vs. 20%, p = 0.05), and higher incidence of chronic graft-versus-host disease (GVHD) (49 vs. 31%, p = 0.04) at 2 years. Cumulative incidence of acute GVHD grade 2-4 at 6 months was not significantly different (30 vs. 23%, p = 0.2). OS for 9/10 MUD with no PIRCHE was similar to 10/10 MUD (57 vs. 55%). In multivariate analysis, PIRCHE retained negative impact on OS (RR 1.5, 95% CI 1.0-2.1, p = 0.03) and NRM (RR 1.7, 95% CI 1.0-2.9, p = 0.03). To the best of our knowledge, for the first time, we show the association of PIRCHE and survival outcome after allo-HSCT. The PIRCHE model, if validated in an independent cohort, may allow selection of permissible HLA mismatches that enable improved transplant outcome.

AB - There is no established standard for selection of mismatched unrelated donors. Indirect recognition of HLA mismatches can be predicted using the model of "Predicted Indirectly ReCognizable HLA Epitopes" (PIRCHE). We performed a multicenter retrospective study evaluating the impact PIRCHE on outcome after allogeneic stem cell transplantation (allo-HSCT) from single mismatched (HLA 9/10 matched) unrelated donors. The study cohort included 424 adult recipients of HLA 9/10 matched unrelated donor transplants (9/10 MUD), treated for AML or MDS at 6 transplant centers across Germany. Detection of PIRCHE was associated with lower overall survival (OS) (47 vs. 57%, p = 0.04), higher non-relapse mortality (NRM) (32 vs. 20%, p = 0.05), and higher incidence of chronic graft-versus-host disease (GVHD) (49 vs. 31%, p = 0.04) at 2 years. Cumulative incidence of acute GVHD grade 2-4 at 6 months was not significantly different (30 vs. 23%, p = 0.2). OS for 9/10 MUD with no PIRCHE was similar to 10/10 MUD (57 vs. 55%). In multivariate analysis, PIRCHE retained negative impact on OS (RR 1.5, 95% CI 1.0-2.1, p = 0.03) and NRM (RR 1.7, 95% CI 1.0-2.9, p = 0.03). To the best of our knowledge, for the first time, we show the association of PIRCHE and survival outcome after allo-HSCT. The PIRCHE model, if validated in an independent cohort, may allow selection of permissible HLA mismatches that enable improved transplant outcome.

U2 - 10.1159/000502389

DO - 10.1159/000502389

M3 - SCORING: Journal article

C2 - 31832062

VL - 46

SP - 370

EP - 375

JO - TRANSFUS MED HEMOTH

JF - TRANSFUS MED HEMOTH

SN - 1660-3796

IS - 5

ER -