Prediction of outcomes after second-line treatment for acute graft-versus-host disease

Acute graft-versus-host disease (GVHD) requiring second-line treatment represents a highly morbid complication of allogenic hematopoietic cell transplantation (HCT). Recent studies have defined short-term outcomes after second-line treatment for acute GVHD, but longer-term outcomes have not been well defined. We examined overall survival (OS) and failure-free-survival (FFS) of 216 patient who had HCT who received second-line treatment for acute GVHD. Failure time for FFS was defined as the earliest of death, relapse, or implementation of third-line treatment. Multivariable Cox regression was used to identify risk factors for mortality and failure, and predictive models were derived for 6- and 12-month mortality. Point estimates of OS at 6 and 12 months were 59% (95% confidence interval [CI], 52-65) and 52% (95% CI, 45-68), respectively. Point estimates of FFS at 6 and 12 months were 42% (95% CI, 35-48) and 37% (95% CI, 31-43), respectively. Predictive models for both end points included serum albumin and total bilirubin concentrations at the onset of second-line treatment, patient age at onset of second-line therapy, and a combination of abdominal pain/stage 4 gut involvement. Optimism-corrected areas under the receiver-operator characteristic curve and Brier scores were 77.4 and 0.169 for 6-month mortality, respectively, and 80.0 and 0.169 for 12-month mortality. We identify risk factors associated with mortality and failure after second-line treatment of acute GVHD, provide historical benchmarks for assessment of FFS and OS in other studies, and propose predictive models for 6- and 12-month mortality that could be used to generate population-specific benchmarks.