Haploidentical Stem Cell Transplantation With Post-Transplantation Cyclophosphamide for Aggressive Lymphomas: How Far Have We Come and Where Are We Going?

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) offers universal donor availability and can potentially cure relapsed or primary refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). However, a conditioning regimen intensity that balances the graft-versus-lymphoma (GvL) effect with regimen-related toxicities (RRTs) has not yet been optimized. Limited data exist on the management of relapse, which is common post-transplant. Few prospective or randomized control trials have been conducted on lymphoma patients undergoing haplo-HSCT. Therefore, the current review aims to summarize published retrospective data in the field to help guide clinical decision making for high-risk patients. Retrospective studies in the field are characterized by variability in patient population and sample sizes, eligibility criteria, number of prior treatments (e.g., chemotherapy, radiation therapy, and autologous transplant), graft source (bone marrow or peripheral blood), as well as choice and intensity of the conditioning regimen (non-myeloablative, reduced intensity, or myeloablative). Nonetheless, common themes that emerge from the literature include: 1) Enhanced donor availability and selection with haplo-HSCT with success in heterogeneous patient populations; 2) Outcomes that are comparable if not superior to matched related (MRD) or unrelated (MUD) donor transplants; 3) The benefit of PTCy for reducing incidence of relapse and chronic graft-versus-host disease (GvHD); 4) Presence of co-morbidities leading to poorer transplant-related outcomes; and 5) The need for novel approaches to address disease relapse, particularly for patients with active disease at the time of transplant. Excellent transplant-related outcomes with haplo-HSCT with PTCy have been seen for HL and NHL based on retrospective data. Further studies are needed to determine integration with advanced cellular therapy techniques, such as chimeric antigen receptor (CAR) T-cell, antibody drug conjugates, and checkpoint inhibitors. Graft manipulation may be another avenue for future research.