Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation

Posttransplant cyclophosphamide (PT-Cy) is an efficient GVHD prophylaxis but has not been extensively evaluated in mismatched unrelated donor (MMUD) allo-HSCT, for which antithymocyte globulin (ATG) is still considered as a standard. Thus, we evaluated the outcome of MMUD allo-HSCT with PT-Cy (n= 22) and performed a historical comparison with a control group receiving ATG (n= 40) in a single center experience. Compared with the ATG group, the risk of grade 2–4 acute GVHD was significantly lower in the PT-Cy group (HR = 0.12, 95% CI = [0.03–0.48], p= 0.002). No difference was observed in the cumulative incidence of chronic GVHD. The risk of both NRM and relapse was significantly lower in the PT-Cy group (NRM: HR = 0.05, 95% CI = [0.00–0.63], p= 0.021; relapse: HR = 0.31; 95% CI = [0.09–1.10], p= 0.07). Thus, we observed significantly better PFS (HR = 0.22, 95% CI = (0.07–0.65); p= 0.006), OS (HR = 0.24, 95% CI = (0.07–0.84); p= 0.026), and GRFS (HR = 0.37, 95% CI = (0.17–0.80); p= 0.011) in the PT-Cy group. We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT, resulting in a better outcome compared with standard prophylaxis using ATG. This suggests that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approach those observed after HLA matched allo-HSCT.