Graft-versus-Host Disease Induced Graft-versus-Leukemia Effect: Greater Impact on Relapse and Disease-Free Survival after Reduced Intensity Conditioning

Abstract

We studied graft-versus-host disease (GVHD) on relapse, transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS) after allogeneic transplantation for acute myelogenous leukemia (AML) (n = 4224) and myelodysplastic syndrome (MDS) (n = 1517) in 4 groups: without GVHD, acute GVHD (aGVHD) alone, chronic GVHD (cGVHD) alone, and aGVHD + cGVHD. Examining GVHD as a time-dependent covariate, after myeloablative conditioning (MAC), cGVHD and aGVHD + cGVHD were associated with lower relapse (P < .002). TRM was higher in all GVHD groups (P < .0001); DFS and OS were lower with aGVHD ± cGVHD (P < .0001). After reduced-intensity conditioning (RIC), relapse was lower in all GVHD groups (P < .0001); TRM was increased and DFS and OS were reduced with any GVHD (P < .0001). In those surviving disease-free (≥1-year) after MAC, relapse risks were similar in all groups and TRM was higher with any GVHD (P < .0001). DFS and OS were lower with cGVHD and aGVHD + cGVHD (P < .0006). After RIC, relapse was lower (P = .009) and TRM higher (P = .002) only with aGVHD + cGVHD. DFS was similar in all groups and OS worse with aGVHD + cGVHD. After MAC, GVHD has an adverse effect on TRM with early modest augmentation of GVHD-associated graft-versus-leukemia (GVL). With RIC, GVHD-associated GVL may be important in limiting both early and late leukemia recurrence