Improved survival after acute graft-versus-host disease diagnosis in the modern era

Hanna J. Khoury, Tao Wang, Michael T. Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H. Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J. Hayashi, Madan Jagasia, Mark Juckett, Rammurti T. Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C. Schouten, Gerard Socie, Jan Storek, Leo Verdonck, Ravi Vij, William A. Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R. Schultz, Baldeep M. Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala

Acute graft vs. host disease remains a major threat to successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft vs. host disease. We examined outcome following diagnosis of grade II-IV acute graft vs. host disease according to time period, and examine effects according to original graft vs. host disease prophylaxis regimen and maximum overall grade of acute GVHD. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grades II-IV acute graft vs. host disease (n=497 for 1999-2001, n=962 for 2002-2005, n=1,446 for 2006-2010). Median follow-up was 144 (4-174), 97 (4-147) and 60 (8-99) months for 1999-2001, 2002-2005, and 2006-2010, respectively. Among the grade II-IV acute graft vs. host disease cohort, there was a decrease in the proportion of grades III-IV acute graft vs. host disease over time with 56%, 47% , and 37% for 1999-2001, 2002-2005, and 2006-2012, respectively (p<0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (p=0.003) and treatment-related mortality (p=0.008) were only noted among those originally treated with tacrolimus-based graft vs. host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft vs. host disease. Survival has improved over time for tacrolimus-treated transplant recipients with acute graft vs. host disease.