EASIX and sC5b-9 for early identification of adults at high risk of developing TA-TMA after allo-HCT.

Transplant-associated thrombotic microangiopathy (TA-TMA) remains a severe complication after allogeneic hematopoietic cell transplantation (allo-HCT). Early prediction of high-risk patients remains challenging, particularly in adults. This prospective observational study consecutively enrolled patients aged >14 years undergoing allo-HCT. TA-TMA was screened and diagnosed according to the harmonization criteria. The 100-day cumulative incidence of TA-TMA was 6.5% (95% CI 4.5-8.9%). Multivariable analyses identified elevated baseline endothelial activation and stress index (EASIX, HR 1.33, p = 0.011) and day 14 sC5b-9 (HR 2.84, p < 0.001) were independently associated with TA-TMA. The optimal cutoff was 217 ng/mL for sC5b-9 and 6.2 for EASIX. Using the cutoffs for the combined EASIX and sC5b-9, patients were stratified into low-, intermediate-, and high-risk groups, with corresponding 100-day incidences of 2.2%, 7.1%, and 32.4%. Compared with the low-risk group, the intermediate- and high-risk groups showed increased risk of TA-TMA (HR 3.29, 95% CI 1.39-7.79; HR 14.32, 95% CI 5.62-36.50, respectively). The risk stratification system showed moderate discrimination, with a time-dependent AUC of 0.75 (95% CI 0.66-0.84). Therefore, baseline EASIX and day14 sC5b-9 were significantly associated with TA-TMA, and their combination may improve early identification of adult patients at high-risk of developing TA-TMA.

trial registrationName of the registry: ClinicalTrials.gov. Trial registration number: NCT06102694. The date that we registered the trial: 10/22/2023. URL of trial registry record: https://clinicaltrials.gov/study/NCT06102694?cond=NCT06102694&rank=1 .