Graft-versus-host disease is not associated with reduced incidence of relapse following haploidentical stem cell transplantation with post-transplant cyclophosphamide for acute lymphoblastic leukaemia: A study on behalf of the Acute Leukaemia Working Party of European Society for Blood and Marrow Transplantation

Abstract

The graft-versus-leukaemia effect (GVL) is closely associated with graft-versus-host disease (GVHD) after human leucocyte antigen (HLA)-matched allogeneic stem-cell transplantation (SCT) in acute lymphoblastic leukaemia (ALL). However, there are no data on this association following haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We assessed the impact of acute and chronic GVHD on haploSCT outcomes in 516 adult ALL patients. The cumulative incidence of acute GVHD grade II-IV and III-IV, chronic GVHD and extensive chronic GVHD was 33.3%, 11.7%, 35.3% and 11.8% respectively. The 2-year relapse incidence (RI), non-relapse mortality (NRM) and overall survival (OS) were 27.1%, 17.3% and 64.4% respectively. The time-dependent hazard ratios (HRs) of acute GVHD grade II, grade III-IV, limited and extensive chronic GVHD associated with RI were 0.92 (95% confidence interval [CI] 0.58-1.48, p = 0.74), 0.57 (95% CI, 0.27-1.22, p = 0.15), 1.06 (95% CI, 0.62-1.82, p = 0.83) and 0.95 (95% CI, 0.42-2.17, p = 0.91) respectively. Acute GVHD grade III-IV and extensive chronic GVHD were associated with higher NRM (hazard ratio [HR] 1.95 [95% CI, 1.09-3.48, p = 0.002] and 3.3 [95% CI, 1.41-7.73, p = 0.006]) and reduced OS (HR 1.91 [95% CI, 1.07-3.39, p = 0.03] and 3.27 [95% CI, 1.4-7.66, p = 0.006]) respectively. In conclusion, acute and chronic GVHD are not statistically associated with reduced RI after haploSCT with PTCy in ALL. Higher GVHD grades are associated with higher NRM and lower OS.

Keywords: acute lymphoblastic leukaemia; graft‐versus‐host disease; graft‐versus‐leukaemia effect; haploidentical transplantation; post‐transplant cyclophosphamide.