New Approaches to Allogeneic Haematopoietic Cell Transplantation

Abstract

Allogeneic haematopoietic cell transplantation is a potentially curative therapeutic option for all haematologic malignancies; however, it is a double-edged sword that may result in significant mortality and morbidity. In recent years, there have been groundbreaking advances in the availability of stem cell sources, emerging strategies for choosing the best donor, graft-versus-host disease (GVHD) prevention, and supportive care. Ultra-high-resolution next-generation sequencing technology has been introduced to obtain more information on human leucocyte antigen (HLA) typing, making it possible to access the best-matched donors. Functional HLA matching with T cell-epitopes 3 and 4, and the "delta functional distance"scoring system, may help with the graft-versus-leukaemia (GLV)-GVHD counterbalance, driving the immune reaction in the direction of GVL. More effective GVHD prophylaxis (post-transplant cyclophosphamide and anti-thymocyte globulin) makes it possible to reach a broader donor diversity, in terms of unrelated and haploidentical settings. Ex vivo stem cell expansion with numerous small molecules (StemRegenin 1, TAT-BMI1, nicotinamide, valproic acid) can improve engraftment and immune reconstitution rates in umbilical cord blood transplantation. Ruxolitinib, ibrutinib, vedolizumab, alpha-1 antitrypsin, and mesenchymal stromal cells have shown promising results in the treatment of acute and chronic GVHD. Letermovir and maribavir have also shown encouraging results in cytomegalovirus reactivation prophylaxis. This article summarizes the current state of art and paradigm shifts in allogeneic haematopoietic cell transplantation.