Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Different Non-T-Cell Depletion Protocols

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as a critical treatment for hematological diseases. However, challenges, such as graft rejection and graft-versus-host disease (GVHD), have historically been faced with this procedure. Immune reconstitution (IR) has been shown to have profound effects on posttransplantation complications, such as relapse, infections, and GVHD. Recent advances in non-T-cell depletion protocols including the Beijing protocol and Baltimore protocol have significantly influenced the outcomes of haplo-HSCT by improving IR. Clinical studies and multiomic analyses have revealed that different protocols offer distinct mechanisms for IR patterns and further influence clinical outcomes. However, there is a lack of comprehensive reviews that systematically link the differences in IR between two protocols to their clinical outcomes, which leaves a critical gap in understanding the optimal strategies for IR in haplo-HSCT. This review provides an analysis of IR following haplo-HSCT with different protocols; it compares the clinical outcomes of various protocols, addresses the role of each immune cell subset in influencing outcomes and discusses emerging strategies aimed at improving IR. This review highlights the importance of ongoing research for improving immune reconstitution strategies, ultimately reducing posttransplant complications and offering targeted treatments to improve patient outcomes.