Using a murine haploidentical BMT model, we recently showed that peritransplant administration of glucocorticoid (GC) redistributed donor T cells from the gastrointestinal tract to bone marrow, which resulted in a significant reduction of GVHD while promoting GVL effects. Furthermore, in a retrospective clinical study of patients with AML undergoing transplantation in non-remission, we also showed that haploidentical stem cell transplantation (haplo-SCT) using peritransplant GC administration led to a significantly lower relapse rate and better overall survival rate compared with haplo-SCT using post-transplant cyclophosphamide. In the present study, using the same dataset of patients undergoing GC haplo-SCT, we retrospectively compared with patients with AML undergoing transplantation in non-remission using 3 other donor types: matched sibling donor (MSD), matched unrelated donor (MUD), and umbilical cord blood (UCB). For GC haplo-SCT, 44 patients underwent PBSCT in a single center (Hyogo College of Medicine), with the conditioning treatment consisting of fludarabine, melphalan, anti-thymocyte globulin (2.5 mg/kg), and TBI 3 Gy. Methylprednisolone was given from the start of conditioning treatment, and the GVHD prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). The transplant outcomes were compared with data of 1889 patients undergoing MSD-SCT (n=449), MUD-BMT (n=493), or UCB transplantation (UCBT) (n=947) in non-CR, which were extracted from the TRUMP data, the largest data registry in Japan. For donor engraftment, significantly faster neutrophil and platelet engraftment was achieved with GC haplo-SCT compared with allo-SCT using the 3 other donor types. Neutrophil engraftment was achieved at a median of 10 days for GC haplo-SCT, and 20 days for MSD-, MUD-, and UCB-transplants. Platelet engraftment was achieved at a median of 19.5 days for GC haplo-SCT, 42 days for MSD-SCT and MUD-BMT, and 43 days for UCBT, respectively. The incidence of grade II-IV acute GVHD was lower after allo-SCTs using MSD (HR=0.465, p=0.003), MUD (HR=0.524, p=0.010), and UCB (HR=0.647, p=0.067) compared with GC haplo-SCT. There was no significant difference in the incidence of chronic GVHD between GC haplo-SCT and allo-SCT using the other 3 donor types. Regarding relapse, GC haplo-SCT was associated with a significantly lower risk compared with MSD-SCT (p<0.001), or MUD-BMT (p=0.004). GC haplo-SCT tended to have a lower risk compared with UCBT (p=0.063). Especially, all the 43 evaluable GC haplo-SCT recipients achieved CR after transplantation, whereas 23.9, 22.8, and 27.0% of patients who underwent MSD-SCT, MUD-BMT, and UCBT could not achieve CR after transplantation, respectively. Regarding non-relapse mortality, GC haplo-SCT was associated with a significantly higher risk compared with MUD-BMT (p=0.014), and tended to have a higher risk compared with MSD-SCT (p=0.061). There was no significant difference between GC haplo-SCT and UCBT (p=0.600). Allo-SCTs using MSD (HR: 2.548, p<0.001), MUD (HR: 2.134, p=0.005), and UCB (HR: 2.376, p=0.001) lead to significantly higher overall mortality compared with GC haplo-SCT; the adjusted overall survival at 3 years was 19.8% for MSD, 26.1% for MUD, 28.0% for UCB, and 65.1% for GC haplo. Thus, GC haplo-SCT is a promising treatment option for patients with AML with a high leukemic burden.Copyright © 2023. Published by Elsevier Inc.
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