Hematopoietic stem cell transplant with HLA-mismatched grafts: impact of donor, source, conditioning, and graft versus host disease prophylaxis

Introduction: Allogeneic hematopoietic cell transplantation is frequently used to treat malignant and non-malignant conditions, and many patients lack a human leukocyte antigen (HLA) matched related or unrelated donor. For those patients, available alternative graft sources include HLA mismatched unrelated donors, cord blood, or haplo-identical donors. These graft sources have unique characteristics and associated outcomes requiring graft-specific variations to conditioning regimens, graft-versus-host disease prophylaxis, and post-transplant care.Areas covered: This manuscript will cover approaches in selecting donors, conditioning regimens, graft versus host disease prophylaxis, post-transplant care, and ongoing clinical trials related to mismatched grafts.Expert commentary: In the setting, haplo-identical grafts are increasingly popular due to low graft versus host disease (GVHD) risk and control of cellular dose. We recommend young male donors, utilizing bone marrow with post-transplant cyclophosphamide for GVHD prophylaxis. Cord blood transplant is appropriate for young healthy patients, and we recommend 6/8 HLA matched grafts with at least 2.0 × 107/kg total nucleated cell dose. For mismatched unrelated donors we recommend young male donors, utilizing bone marrow with in vivo T-cell conditioning with post-transplant cyclophosphamide, alemtuzumab, or ATG. With these transplants, significant post-transplant surveillance and infectious prophylaxis is key to reducing treatment-related mortality.