Human Leukocyte Antigen-Haploidentical Haematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide for Paediatric Haematological Malignancies

Simple Summary Human leukocyte antigen (HLA)-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) for haematological malignancies is an HSCT modality that has become widespread worldwide in the last 20 years and is also widely used in children. Haplo-HSCT with PTCY in adult patients with haematologic malignancies has comparable outcomes with HLA-matched unrelated donor HSCT. This review article comprehensively describes the current progress in haplo-HSCT with PTCY for paediatric haematological malignancies. The current state and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, and the concomitant graft-versus-host disease prophylaxis other than PTCY are also extensively discussed. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies.Abstract The use of human leukocyte antigen (HLA)-haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for patients with high-risk haematologic malignancies. However, this strategy is currently used more frequently for standard-risk, transplant-eligible paediatric haematological malignancies. It has recently been recognised in adults that the transplant outcomes after PTCY-based HLA-haploidentical HSCT are comparable with those achieved after HLA-matched HSCT. Therefore, even in children, parental donors who are HLA-haploidentical donors and cord blood are currently considered the next donor candidates when an HLA-matched related or unrelated donor is unavailable. This review addresses the current status of the use of haplo-HSCT with PTCY for paediatric haematologic malignancies and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, the concomitant graft-versus-host disease prophylaxis other than PTCY, and the pharmacokinetic study of CY and CY metabolites. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies.