Allogeneic Stem Cell Transplant With Alpha/Beta T AND B Cell Depletion for Hematologic Malignancies

This is a single-arm, prospective study evaluating the safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) using ex vivo α/β T-cell-depleted and CD19+ B-cell-depleted peripheral blood stem cell grafts processed with the CliniMACS device in patients with hematologic malignancies who lack matched related donors. Participants will receive mobilized peripheral blood stem cells from unrelated or partially matched related donors. The collected stem cell products will undergo ex vivo manipulation using the CliniMACS system to selectively deplete T-cell receptor (TCR) α/β-positive T lymphocytes and CD19+ B cells while preserving CD34+ hematopoietic stem cells, natural killer (NK) cells, and γ/δ T cells. This selective depletion strategy aims to reduce the risk of graft-versus-host disease (GVHD) while maintaining engraftment potential and immune function. All patients will receive myeloablative conditioning with either total body irradiation-based or busulfan-based regimens, with anti-thymocyte globulin administered in selected patients based on donor type and clinical indication. Routine post-transplant pharmacologic GVHD prophylaxis is not planned but may be administered at the discretion of the treating physician if clinically indicated. The primary objectives are to evaluate engraftment (including incidence of primary graft failure and time to neutrophil and platelet recovery), incidence and severity of acute and chronic GVHD, treatment-related mortality, and one-year leukemia-free survival. Secondary objectives include assessment of immune reconstitution, incidence of viral infections (including CMV, EBV, adenovirus, and HHV-6), and correlation of outcomes with donor and recipient killer immunoglobulin-like receptor (KIR) typing. The study will enroll approximately 110 patients over a 10-year period, with outcomes analyzed descriptively using estimates of event rates and confidence intervals. The goal of this study is to determine whether selective α/β T-cell and CD19+ B-cell depletion using the CliniMACS system improves transplant outcomes by reducing GVHD while enabling durable engraftment and enhanced immune recovery in patients receiving alternative donor transplants.