Exploration of In Vivo T-cell Depletion protocols in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.

Graft-versus-host disease (GVHD) remains a major concern following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two principal in vivo T-cell depletion (TCD) strategies-post-transplant cyclophosphamide (PTCY)-based and anti-thymocyte globulin (ATG)-based GVHD prophylaxis-have effectively mitigated this challenge. In recent years, PTCY has expanded beyond haploidentical HSCT to include matched related donor (MRD), matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HSCT, resulting in favorable outcomes. ATG-based regimens have been optimized in terms of dosing and timing across various transplant settings. Individualized ATG administration shows potential in overcoming the highly heterogeneous pharmacokinetics. Some prospective studies have explored the combined use of ATG and PTCY in haploidentical and MUD HSCT. Only a few randomized controlled trials (RCTs) have compared ATG and PTCY head-to-head, and high-level evidence remains scarce. Ongoing clinical trials are expected to clarify which in vivo T-cell depletion protocol is better, and whether adjustments in timing, dose, or combination can yield better outcomes for patients.