Haploidentical Allogeneic Stem Cell Transplantation in Sickle Cell Disease: a Systematic Review and Meta-analysis.

Abstract Background Allogeneic hematopoietic stem cell transplantation (SCT) is the only established curative treatment option for patients with sickle cell disease (SCD). However, lack of HLA-identical sibling donors is a limiting factor. Haploidentical related donors are a promising pool of donors, potentially extending SCT as a curative treatment option to a larger group of patients with no other meaningful treatment options for their severe SCD. In the present study, we aimed to systematically review the results of haploidentical SCT in SCD. Methods A comprehensive search was performed in MEDLINE/Pubmed and Embase up to May 2021. Data was extracted by two reviewers independently and the Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. Fourteen studies met the inclusion criteria. To have an overview of the results of haploidentical SCT, we grouped the studies into myeloablative versus non-myeloablative conditioning as well as in vitro or in vivo (post-transplant cyclophosphamide) T-cell depletion with a subgroup meta-analysis of proportions. Results All studies included were observational cohort studies. Only 3 of these studies reported data of both matched sibling donor (MSD) SCT and haploidentical SCT. Based on a comparative meta-analysis of the three studies that included both haploidentical and MSD transplantation, graft failure was significantly higher in the haploidentical group than in the MSD group (odds ratio 5.3, 95% CI: 1.0 – 27.6). Overall survival was not significantly different between the groups. A subgroup meta-analysis of the results of haploidentical SCT showed relatively low overall pooled proportions of graft failure (7%, 95% CI: 2 – 20), acute (4%, 95% CI: 2 – 12) and chronic (11%, 95% CI: 7 – 16) graft versus host disease. Overall survival was high in all the studies included (91%, 95% CI: 85 – 94). Conclusions Adjustments to the conditioning regimens, robust pre- and post-transplant T-cell depletion and improved supportive care have resulted in reduced graft failure and improved overall survival following haploidentical SCT in patients with SCD. We conclude that the safety of haploidentical SCT in SCD patients has improved significantly and should be considered as a curative option in patients with severe SCD.