Antibiotic risk score for acute graft-versus-host disease Open Access

• An antibiotic risk score predicts the added risk for acute GVHD due to early peri-transplant antibiotic exposures.

Certain antibiotic exposures have been associated with increased rates of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (alloHCT). Using data from 2,023 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 peri-transplant period. Here, we validated the score in an independent, more recent cohort. Data from 297 alloHCT recipients (2022-2023) including 8,382 antibiotic use records (9 antibiotic classes) were analyzed. Median (range) age was 61 (19-78) years. 175 (59%) patients were male. Higher scores predicted a greater added antibiotic-related risk for grade III-IV (severe) aGVHD, with the upper 25% score quantile identifying a distinctly high-risk subset of patients (hazard ratio for the upper 25% risk quantile 2.37 compared to the lower 75%, 95% confidence interval 1.21-4.63, P = 0.01). A similar, though less strong pattern was observed for grade II-IV 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 higher-risk patients 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.