LAUSR

Background In recipients of allogeneic hematopoietic stem cell transplantation (HSCT), organ toxicity is a barrier to administering high-intensity conditioning. We hypothesized that determinants of acute organ toxicity are specific to individual regimens. We sought to characterize these toxicities, evaluate their prognostic implication, and derive predictors of severe toxicity at the regimen level. Methods This retrospective study included adults undergoing first allogeneic HSCT at a single center between 2001 and 2014. Patients received grafts from matched sibling or unrelated donors and received any of the following regimens: Cy/TBI, Bu/Cy, Flu/Bu 12.8 mg, Flu/Bu 6.4 mg, Flu/Treosulfan 36-42 gr/m2, and Flu/Mel 100-140 mg/m2. Studied toxicities included acute kidney injury (AKI) per KDIGO definition and increases in total bilirubin, AST, ALT, and alkaline phosphatase (Alk Phos) per CTCAE grading. The incidence of toxicities from conditioning through 30-days post-HSCT was tabulated. Risk factors for severe organ toxicity were assessed within each regimen using multivariable logistic regressions. Results In a cohort of 707 patients, the main indications were acute leukemia (57%), myelodysplastic syndrome (13%), and aggressive lymphoma (9%). GvHD prophylaxis included methotrexate in 80% of patients, and 56% received ATG. The incidence of AKI and increased serum bilirubin in each regimen is shown in Figure 1A/B, respectively. Sinusoidal-obstructive syndrome (6% overall) accounted for only 17% of gr. ≥ 3 bilirubinemia in the entire cohort. Elevations in AST, ALT, and Alk Phos of gr ≥ 3 were not common ( Conclusion Allogeneic transplantation recipients are at high risk for acute organ damage. We describe patterns of renal and liver toxicity across several regimens. Determinants of acute severe organ toxicity, defined as those associated with short-term mortality, are regimen dependent. Our findings suggest these factors should be considered in selecting the preparative regimen. While requiring validation, the newly-defined composite endpoint of acute severe organ toxicity (ASOT) may be valuable in studying transplantation strategies.