Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality

Abstract

Whether the hematopoietic cell transplantation comorbidity index (HCT-CI) can provide prognostic information about development of acute graft-versus-host disease (GVHD) and subsequent mortality is unknown. Five institutions contributed information on 2985 patients given human leukocyte antigen-matched grafts to address this question. Proportional hazards models were used to estimate the hazards of acute GVHD and post-GVHD mortality after adjustment for known risk variables. Higher HCT-CI scores predicted increased risk of grades 3 to 4 acute GVHD (P < .0001 and c-statistic of 0.64), and tests of interaction suggested that this association was consistent among different conditioning intensities, donor types, and stem cell sources. Probabilities of grades 3 to 4 GVHD were 13%, 18%, and 24% for HCT-CI risk groups of 0, 1 to 4, and ≥5. The HCT-CI was statistically significantly associated with mortality rates following diagnosis of grade 2 (hazard ratio [HR] = 1.24; P < .0001) or grades 3 to 4 acute GVHD (HR = 1.19; P < .0001). Patients with HCT-CI scores of ≥3 who developed grades 3 to 4 acute GVHD had a 2.63-fold higher risk of mortality than those with scores of 0 to 2 and did not develop acute GVHD. Thus, pretransplant comorbidities are associated with the development and severity of acute GVHD and with post-GVHD mortality. The HCT-CI could be useful in designing trials for GVHD prevention and could inform expectations for GVHD treatment trials.

Figure 1

Probabilities of grades 3 to 4 acute GVHD as stratified by the HCT-CI scores among 2985 recipients of allogeneic HCT. Patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5 had 13%, 18%, 18%, and 24% probabilities, respectively, of grades 3 to 4 acute GVHD at 120 days after HCT.

Figure 2

Kaplan Meier estimates of overall survival. A landmark analysis dating from the onset of grade 2 (number of patients = 1191) (A) or grades 3 to 4 (number of patients = 511) (B) acute GVHD as stratified by the HCT-CI scores. Patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5 had 3-year rates of survival of 78%, 58%, 42%, and 30%, respectively, following diagnosis of grade 2 acute GVHD. The figures for survival rates following diagnosis of grades 3 to 4 acute GVHD were 54%, 39%, 21%, and 16%, respectively.