Improved Treatment-Related Mortality and Overall Survival of Patients with Grade IV Acute GVHD in the Modern Years

Abstract

The impact of advances in supportive care and hematopoietic stem cell transplantation (HSCT) practices on the outcomes of patients who develop grade III or IV acute graft-versus-host disease (GVHD) is unknown. We performed a retrospective analysis of 427 patients with overall grade III or IV acute GVHD treated at 2 partner institutions between 1997 and 2012. We compared treatment-related mortality (TRM) and overall survival (OS) in 2 cohorts based on the year of transplantation, 1997 to 2006 (n = 222) and 2007 to 2012 (n = 205), using multivariate analysis, adjusting for significant patient-, disease-, and transplantation-related factors. Recipient age, reduced-intensity conditioning, unrelated donor, and peripheral blood stem cell grafts in the patients with grade III or IV acute GVHD increased over time. In the unadjusted analysis, 12-month OS increased over time (30% in 1997 to 2006 versus 42% in 2007 to 2012; P = .003) reflecting a decrease in TRM (58% in 1997 to 2006 versus 38% in 2007 to 2012; P = .0002), and an increase in PFS (29% in 1997 to 2006 versus 43% in 2007 to 2012; P = .002). On multivariate analysis, the period of transplantation remained a significant predictor for OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54 to 0.94; P = .02), progression-free survival (PFS) (HR, 0.70; 95% CI, 0.52 to 0.94; P = .02), and TRM (HR, 0.57; 95% CI, 0.39 to 0.82; P = .002). In subgroup analysis, these differences were observed mainly in patients with grade IV acute GVHD. The outcomes of patients who develop overall grade III or IV acute GVHD after allogeneic HSCT has improved over time, with lower TRM and improved OS. This improvement in outcomes was seen primarily in patients with grade IV acute GVHD.

Keywords: Allogeneic HCT; GVHD; Survival; Transplant-related mortality.