Haploidentical Transplantation with Modified Post-transplantation Cyclophosphamide for Patients with Primary Aplastic Anemia: A Multicenter Experience

Abstract

Aplastic anemia (AA) is a life-threatening hematological disorder that can be cured by hematopoietic stem cell transplantation. Haploidentical transplantation becomes an alternative choice for patients in the absence of a matched sibling donor. We used a retrospective study aimed to confirm the feasibility of busulfan-based modified post-transplantation cyclophosphamide (PTCY) strategy in haploidentical hematopoietic stem cell transplantation for AA patients. We analyzed the outcomes of 27 patients from 3 clinical centers who had undergone haploidentical transplantation between October 2018 and July 2020. The modified condition regimen consisted of anti-thymoglobulin/antilymphocyte globulin, fludarabine, busulfan and low-dose cyclophosphamide, and high-dose cyclophosphamide, mycophenolate mofetil (MMF) and tacrolimus were administered as graft versus host disease (GVHD) prophylaxis after transplantation. The median follow-up time was 370 (range 65-721) days. One patient developed primary graft failure, and successful engraftment was observed in 96.29% (95% confidence interval [CI], 93.45%-97.91%) of patients. The median times for neutrophil and platelet engraftment were 13 (range 11-18) days and 13 (range 11-28) days, respectively. The most common regimen-related toxicity was bladder toxicity, followed by stomatitis and gastrointestinal toxicity. The cumulative incidence of grade II-IV aGVHD was 25.93% (95% CI, 5.84%-52.64%), whereas the cumulative incidence of grade III-IV aGVHD was 7.4% (95% CI, 0%-52.16%). Chronic GVHD was observed in 3 patients by the end of follow-up. All 27 patients are alive, with a failure-free survival rate of 96.30% (95% CI, 6.49%-99.47%) and GVHD relapse-free survival rate of 88.89% (95% CI, 69.39%-96.28%). Virus reactivation was comparable, with rates of 53.54% for cytomegalovirus (CMV) reactivation and 41.57% for Epstein-Barr virus, but the CMV diseases and post-transplantation lymphoproliferative disorder were rare. Our study using haploidentical transplantation with modified PTCY demonstrated an encouraging result with prolonged survival and reduced complications for aplastic anemia patients.

Keywords: Aplastic anemia; GVHD prophylaxis; Haploidentical; Post-transplantation cyclophosphamide; Transplantation.