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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1413927
This article is part of the Research Topic Community Series in Immune Tolerance Post Allogeneic Hematopoietic Cell Transplantation: Volume II View all 3 articles

Impact of Inhibitory KIR Ligand Mismatch and Other Variables on Outcomes Following Myeloablative Posttransplant Cyclophosphamide-Based T Cell-Replete Haploidentical Bone Marrow Transplantation

Provisionally accepted
Sarah Lindner Sarah Lindner 1,2Emilia Salzmann Emilia Salzmann 2Hubert Serve Hubert Serve 2Peter Bader Peter Bader 2Jan-Henning Klusmann Jan-Henning Klusmann 2Christian Seidl Christian Seidl 3Joachim Schwaeble Joachim Schwaeble 3Gesine Bug Gesine Bug 2Evelyn Ullrich Evelyn Ullrich 2*
  • 1 Charité University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany
  • 2 University Hospital Frankfurt, Frankfurt, Hesse, Germany
  • 3 Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Services, Frankfurt, Hesse, Germany

The final, formatted version of the article will be published soon.

    Post-transplant cyclophosphamide (PTCy) has revolutionized the landscape of human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (haplo-HCT), providing a pivotal therapeutic option for patients with hematological malignancies who lack an HLA-matched donor. In this retrospective analysis involving 54 adult patients undergoing PTCy-based haplo-HCT, we evaluated the impact of inhibitory killer immunoglobulin-like receptor (KIR)/HLA mismatch, alongside patient, donor, and transplant factors, on clinical outcomes within a homogeneous cohort characterized by a myeloablative conditioning regimen and bone marrow graft. With a median followup of 73.2 months, our findings reveal promising outcomes: the six-year overall survival, relapse-free survival, and graft-versus-host disease (GVHD) and relapse-free survival rates were 63% (95% CI, 51-79), 58% (95% CI, 46-74), and 42% (95% CI, 30-58), respectively. Notably, the cumulative incidence of relapse and non-relapse mortality at six years post-haplo-HCT were 15% (95% CI, 9-24) and 12% (95% CI, 6-26), respectively. Acute GVHD at day 100 post-transplantation occurred with a cumulative incidence of 33% (95% CI, 22-49%) for grade II-IV and 9% (95% CI, 3-23%) for grade III-IV. Furthermore, 41% of patients developed chronic GVHD within one year post-transplantation, distributed as follows: 28% mild, 9% moderate and 4% severe. Within our cohort, several variables were associated with outcomes following PTCy-based haplo-HCT. However, inhibitory KIR/HLA mismatch did not influence these outcomes.

    Keywords: T cell Repleted Haploidentical Bone Marrow Transplantation, posttransplant cyclophosphamide, Inhibitory KIR Ligand Mismatch, Recipient/Donor Variables, Immune reconstitution

    Received: 08 Apr 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Lindner, Salzmann, Serve, Bader, Klusmann, Seidl, Schwaeble, Bug and Ullrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Evelyn Ullrich, University Hospital Frankfurt, Frankfurt, 60590, Hesse, Germany

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