Antibiotic risk score for acute graft-versus-host disease

Certain antibiotic exposures have been associated with increased rates of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplant (alloHCT). Using data from 2023 alloHCTs performed at our center (2010-2021), we recently developed an antibiotic risk score based on antibacterial antibiotic exposure between days -7 and +30 of alloHCT. The objective was to estimate the added risk for aGVHD due to exposures to antibiotics in the early peritransplant period. Here, we validated the score in an independent, more recent cohort. Data from 297 recipients of alloHCT (2022-2023) including 8382 antibiotic use records (9 antibiotic classes) were analyzed. Median (range) age was 61 (19-78) years, and 175 (59%) patients were male. Higher scores predicted a greater added antibiotic-related risk for grade 3 to 4 (severe) aGVHD, with the upper 25% score quantile identifying a distinctly high-risk subset of patients (hazard ratio for the upper 25% risk quantile was 2.37 compared with the lower 75%; 95% confidence interval, 1.21-4.63; P = .01). A similar, though less strong, pattern was observed for grade 2 to 4 aGVHD. A free online antibiotic risk calculator was developed, identifying antibiotic exposures associated with higher added risk for severe aGVHD. In addition to its potential future use to identify patients who were at higher risk for aGVHD due to antibiotic exposures, the antibiotic-based risk score provided here can be included as a single continuous covariate in multivariable analysis of future GVHD prophylaxis trials.