Single agent Cyclosporine for Graft versus host disease prophylaxis in patients with acquired Aplastic Anemia receiving fludarabine based conditioning

Abstract Background Cyclosporine (CsA) combined with short course methotrexate (MTX) is considered standard of care graft versus host disease (GVHD) prophylaxis for severe aplastic anemia (AA) patients transplanted using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu) based conditioning. Methods We conducted a single center retrospective analysis of acquired AA (n=106) patients undergoing MRD transplantation from July 2007 till January 2019. All patients received Flu-Cy-ATG conditioning and single agent CsA as graft versus host disease (GVHD) prophylaxis. Results Median age of study cohort was 20 years (range 3-52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range 2.8-62). Graft source was bone marrow harvest (BMH) in 71 (68%), combined bone marrow and peripheral blood stem cells (PBSC) in 34(31%) and PB alone in 1(1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% CI: 87.3-97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI: 84-96%). Cumulative incidence of primary graft failure (PGF) at day 28 was 6.6% (95% CI: 4-8%) while secondary graft failure occurred at median of 190 days (range 90-415) at cumulative incidence of 3.7% (95% CI: 2-5%). Cumulative incidence of acute GVHD grade II-IV at day 100 was 3.8% (95% CI: 1.4-9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI: 2.6-15%). Median follow up post-transplant was 61 months (range 6-144). Overall survival was 84.9%; disease free survival 80.2% and GVHD free relapse free survival was 76.3%. Conclusion This study indicates that single agent cyclosporine is a feasible option for GVHD prophylaxis in MRD HSCT using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.