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.

• Authors: Daniel Weisdorf, Mei-Jie Zhang, Mukta Arora, Mary M Horowitz, J Douglas Rizzo, Mary Eapen
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 18 Issue 11 Pg. 1727-33 (Nov 2012) ISSN: 1523-6536 [Electronic] United States
• PMID: 22766220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Myeloablative Agonists

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Child
• Chronic Disease
• Disease-Free Survival
• Female
• Graft vs Host Disease (immunology, mortality, therapy)
• Graft vs Leukemia Effect
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Myeloid, Acute (immunology, mortality, therapy)
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Myelodysplastic Syndromes (immunology, mortality, therapy)
• Prospective Studies
• Recurrence
• Transplantation Conditioning (methods)
• Transplantation, Homologous