A single dose of posttransplant cyclophosphamide (PTCy) provided effective prophylaxis against acute graft-versus-host disease (GVHD) in patients who underwent hematopoietic stem cell transplantation (HSCT) using human leukocyte antigen (HLA) matched-unrelated donors. These study findings were reported in the American Journal of Hematology.
For patients undergoing allogeneic HSCT with haploidentical donors, PTCy as a component of GVHD prophylaxis has shown efficacy, and PTCy has also been effective in patients undergoing HLA matched-related and matched-unrelated bone marrow transplantation. However, outcomes with the use of PTCy have been mixed in different settings, and its use may raise the risk of infectious complications.
In this single-arm trial (ClinicalTrials.gov Identifier: NCT02065154), patients who had HLA matched-unrelated donors underwent myeloablative peripheral blood stem cell allogeneic HSCT. Following HSCT, they received a single dose of PTCy with tacrolimus and mycophenolate mofetil as GVHD prophylaxis. The primary study endpoint was determination of the cumulative incidence of grade 2-4 acute GVHD at day 100 after allogeneic HSCT. Cumulative incidence of chronic GVHD and multiple survival outcomes were among the secondary endpoints.
The study enrolled 39 patients, among whom 36 had 8/8 HLA matched-unrelated donors, and 3 had 7/8 HLA matched-unrelated donors. One fatality occurred before engraftment within the first 30 days following HSCT, but the other 38 patients (97%) achieved engraftment.
The day-100 cumulative incidence of grade 2-4 acute GVHD was 30% (95% CI, 15.2%-40.1%), and grade 3-4 acute GVHD was 5% (95% CI, 2.1%-8.2%). The cumulative incidence of mild chronic GVHD at 2 years was 15% (95% CI, 7.1%-23.3%), moderate chronic GVHD was 15% (95% CI, 8.4%-23.3%), and severe chronic GVHD was 18% (95% CI, 12.6%-27.4%).
Nonrelapse mortality occurred with a 2-year cumulative incidence of 34% (95% CI, 18.6%-49.6%), and the 2-year cumulative incidence of relapse was 21% (95% CI, 7.6%-33.4%). At 2 years, progression-free survival was an estimated 45% (95% CI, 29.5%-61.3%) and overall survival an estimated 51% (95% CI, 34.7%-66.5%).
The researchers determined that the protocol using a single dose of PTCy was associated with a low incidence of severe acute GVHD, without raising relapse risk. However, they also determined there was no evidence of a mitigation of chronic GVHD risk compared with a regimen using 2 doses of PTCy.
Jamy O, Innis-Shelton R, Bal S, et al. Phase II clinical trial of one dose of post-transplant cyclophosphamide for graft versus host disease prevention following myeloablative, peripheral blood stem cell, matched-unrelated donor transplantation. Am J Hematol. Published online July 20, 2021. doi:10.1002/ajh.26296