Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA- matched stem-cell transplantation for AML

Abstract

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, the rates of acute GVHD grade II-IV and III-IV, chronic GVHD and extensive chronic GVHD were 23.8%, 7.5%, 37.0% and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall-survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD was associated with lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001) and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5% and 17.7%, respectively. Acute GVHD grade II-IV was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated in contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.