Transplant Cell Ther. 2023 Jun 11:S2666-6367(23)01353-2. doi: 10.1016/j.jtct.2023.06.008. Online ahead of print.
ABSTRACT
INTRODUCTION: Graft-versus host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplant (HCT). We hypothesized that the GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) would be associated with a low incidence of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT.
METHODS: This is a phase II study conducted at the University of Minnesota using a myeloablative regimen of either: (A) total body irradiation (TBI, total dose 1320 cGy, administered in 165 cGy fractions, twice a day from days -4 to -1) or (B) Busulfan 3.2mg/kg daily (cumulative AUC 19,000 – 21,000 μmol/min/L) plus fludarabine 40 mg/m2 once daily days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy (50mg/kg days +3 and +4), Tac and MMF (beginning day +5). The primary endpoint was cumulative incidence of chronic GVHD requiring systemic immunosuppression (IST) at 1-year post-transplant.
RESULTS: From March 2018 – May 2022, we enrolled 125 pediatric and adult patients with a median follow-up of 813 days. The incidence of chronic GVHD requiring systemic IST at 1 year was 5.5%. Grade II-IV acute GVHD occurred in 17.1%; Grade III-IV acute GVHD was 5.5%. Two-year overall survival (OS) was 73.7%, and 2-year graft-versus-host disease-free, relapse-free survival (GRFS) 52.2%. The 2-year cumulative incidence of non-relapse mortality was 10.2% and relapse was 39.1%. There was no statistically significant difference in survival outcomes between recipients of matched versus 7/8 donors.
CONCLUSION: Myeloablative HCT with PTCy/Tac/MMF results in an extremely low incidence of severe acute and chronic GVHD in well-matched allotransplantation.
PMID:37311510 | DOI:10.1016/j.jtct.2023.06.008
