Triple stem cell infusion alleviated graft-versus-host disease and improves outcomes in unmanipulated haploidentical hematopoietic stem cell transplantation.

Abstract

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) provides cure opportunity for patients requiring prompt allogeneic HSCT but failing to identify well-matched donor, but its outcomes are potentially impaired by increased transplant-related mortality (TRM). We performed haplo-HSCT using granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cells (PBSCs), umbilical cord mesenchymal stem cells (UC-MSCs) and third-party unrelated umbilical cord blood (UCB) stem cells. Modified "Beijing protocol" were performed in this study. All of the patients were transplanted by Busulfan or TBI-based regimen. Anti-thymocyte globulin were used to T-cell depletion in vivo. Cyclosporine, mycophenolate mofetil, and short course methotrexate were used to prevent graft-versus-host disease (GVHD). One hundred and sixty-five patients with hematological disorders undergoing haplo-HSCT from Jan 2021 to Nov 2023 were included in this study. The median time of neutrophil engraftment were 12 days (range: 9-25 days), and the median time of platelet engraftment were 13 days (range: 6-50 days). Full haploidentical donor chimerism were obtained within 30 days. No evidence of UCB chimerism was found. Twenty-five patients developed acute GVHD. The incidence of grade II-IV and grade III-IV acute GVHD was 12.73% and 6.67%, respectively. Twenty-eight patients developed chronic GVHD, 10 were limited (6.06%) and 18 were extensive (10.91%). The TRM is total of 26 deaths (15.8%) and the cumulative incidence of relapse (CIR) is total of 17 deaths (11.8%) occurred as of the statistical period. The 2 years overall survival (OS) rate is 72.96%. The median overall survival rate was not reached. Haplo-HSCT performed by PBSCs, UC-MSCs and UCB "triple-infusion" achieved excellent outcomes, and need to explored in a larger cohort.