Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Higher-Risk Myelodysplastic Syndrome

Introduction: Allogeneic hematopoietic cell transplantation is an only potentially curative option for patients with higher-risk myelodysplastic syndrome (MDS). Owing to the advances in treatment strategies including reduced intensity conditioning, graft-versus-host disease (GVHD) prevention and supportive care, more elderly patients or those with comorbidities can proceed to allogeneic HCT. However, the long-term survival rate following allogeneic HCT is reported to be less than 50%, and non-relapse mortality (NRM) rate is still high reaching upto 30%. In this study, we aimed to evaluate the feasibility of using post-transplantation cyclophosphamide (PTCy) as a GVHD prophylaxis in allogeneic HCT for higher-risk MDS patients. We also compared the post-transplantation outcomes of PTCy group and those of historical control who received HCT using anti-thymocyte globulin (ATG).

Methods: Patients with higher-risk MDS or MDS/myeloproliferative neoplasm (MPN) with bone marrow blast ≥ 5% were included in this study. Higher-risk MDS was defined by MDS with International Prognostic Scoring System >1.0 or bone marrow blast ≥ 5% at any time points before HCT. Conditioning regimen consists of busulfan (4-days for patients aged <55 years, 2-days for 55 years), fludarabine. For GVHD prophylaxis, PTCy (50 mg/kg on days 3 and 4), cyclosporine, and mycophenolate mofetil were administered. In historical group, patients received 2- or 4-days of busulfan, fludarabine, and ATG with short course of methotrexate and cyclosporine.

Results: Ninety-two and 144 patients received allogeneic HCT using PTCy and ATG, respectively. The median overall survival were 47.9 and 44.0 months, respectively (P=.383). Cumulative incidence of total and grade II-IV acute GVHD in PTCy and ATG group were 19.6% vs. 37.5% (P=.002), and 2.6% vs. 21.7% (P<.001), respectively. Incidence of total and extensive chronic GVHD (50.0% vs. 49.1%, P=.567; 32.5% vs. 33.4%, P=.581), 1-year NRM (20.8% vs. 22.9%, P=.702), and 2-year relapse (16.0% vs. 18.1%, P=.605) were not different between two groups. Neutrophil and platelet engraftment was significantly faster with ATG than PTCy (median 12 vs. 15 for neutrophil; median 15 vs. 24 days for platelet).

Conclusion: Allogeneic HCT using PTCy as GVHD prophylaxis in higher-risk MDS seems feasible in terms of low rate of acute GVHD and relapse incidence.