Initial liver involvement in acute GVHD is predictive for nonrelapse mortality

Current grading systems in acute graft-versus-host disease (GVHD) are not able to identify patients with poor prognosis at time of onset, because they take into account maximal grade. The aim of this study was to evaluate potential predictors for overall survival at disease onset.

The study sample was composed of 142 allogeneic hematopoietic stem-cell transplant recipients who developed acute GVHD after a myeloablative conditioning regimen. Factors associated with the risk of nonrelapse mortality (NRM) were analyzed with proportional hazard models.

At time of diagnosis, GVHD involved a single organ in the majority of the patients (78%). Initial grade was I in 24%, II or III in 56% of patients. Significant risk factors for NRM were non-HLA matched sibling donor (68% vs. 55%, P=0.05), absence of methotrexate in GVHD prophylaxis (75% vs. 56%, P=0.02), initial liver involvement (80% vs. 56%, P<0.001), time to GVHD more than 24 days (76% vs. 55%, P=0.04), nonhyperacute GVHD (72% vs. 52%, P=0.016), and steroid refractory GVHD (85% vs. 44%, P<0.001). In multivariate analysis, initial liver involvement (hazard ratio 2.45; 95% confidence interval 1.46-4.12) and a non-HLA identical sibling donor (hazard ratio 1.58; 95% confidence interval 1.02-2.43) were independently associated with NRM.

Initial liver involvement was an important clinical predictor and should be considered in patient management.