BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Alloimmunity and Transplantation
HLA-Vaccine Transplantations for Refractory Leukemia: Beyond Double-Unit Cord Blood
Provisionally accepted
- 1Duke-NUS Medical School, Singapore, Singapore
- 2KK Women's and Children's Hospital, Singapore, Singapore
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ABSTRACT: Recent studies in double-unit cord blood transplantation have shown that when the patient (PT) and the losing unit (LU) share an HLA determinant mismatched against the winning unit (WU), leukemia relapse risk declines without added graft-versus-host disease (GvHD), suggesting a potential "HLA-vaccine" effect. Building on this principle, we treated five patients with refractory leukemia using graft combinations beyond cord–cord pairs, including haploidentical–cord (haplo-cord) and haploidentical–haploidentical (haplo-haplo) transplants, purposefully selected for predicted HLA-vaccine effects. All patients had measurable residual disease at transplantation and received reduced-intensity conditioning without total body irradiation. Engraftment occurred in all cases, with durable WU dominance and complete remission achieved within one month. Transient chimerism of the LU suggests a rapid, immune-mediated graft-versus-graft (GvG) and potentially graft-versus-leukemia (GvL) effect, triggered by shared, mismatched HLA allotypes. These findings imply that HLA-vaccine transplantation may be feasible across diverse graft pairings, offering a novel therapeutic avenue for refractory leukemia
Keywords: HLA, Leukemia, Allogeneic stem cell transplanation, graft verses leukemia response, alternative donor sources
Received: 16 Oct 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Leung, Seng, Pham, Chong and Tan. 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: Wing Leung, leung.wing.hang@singhealth.com.sg
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