Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft
Key claim: Reduced intensity conditioning followed by T-cell depleted, immunoregulatory-enriched donor grafts from matched or haploidentical donors may facilitate post-transplant immune reconstitution while minimizing GVHD in older or unfit patients with advanced hematologic malignancies.
Abstract
Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.
Why this matters
Older and unfit MPN patients are frequently denied transplant due to GVHD and toxicity risk, so strategies that decouple GVHD from graft-versus-tumor activity are central to expanding eligibility. T-cell depletion enriched for immunoregulatory populations, paired with RIC, offers a graft-engineering lever distinct from the dominant pharmacologic GVHD-prophylaxis paradigms (JAK inhibitors, PTCy) currently being tested in this area. If validated, it could broaden donor selection — particularly for haploidentical donors — in patients otherwise excluded from allo-HCT.