Infection-associated sTNFR1 elevation predicts post-transplant thrombotic microangiopathy in severe aplastic anemia

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe and potentially fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early identification of patients at risk is essential for timely intervention and improved outcomes. This study aimed to identify biomarkers capable of predicting the early risk of TA-TMA in patients with severe aplastic anemia (SAA) undergoing allo-HSCT.

In a prospective nested case-control study of patients with SAA undergoing allo-HSCT, blood samples were collected before pretreatment, before infusion, and on days +7, +14, and +28. TA-TMA cases were matched 1:2 to controls. Biomarkers were compared, and predictive performance was assessed using Receiver operating characteristic analysis and Cox models.

TA-TMA was associated with markedly higher mortality (59% vs. 1.3%). Soluble tumor necrosis factor receptor 1 (sTNFR1) consistently showed the strongest predictive ability, including before pretreatment (area under the curve 0.76; 95% CI, 0.60-0.91). A cutoff of 1.93 ng/mL yielded 0.88 specificity and 0.69 sensitivity. Elevated pretreatment sTNFR1 (≥1.93 ng/mL) predicted TA-TMA (hazard ratio, 6.78; 95% CI, 2.26-20.3; p < 0.001) and death (21.44; 95% CI, 2.57-179; p = 0.005). 19 had pre-transplant infections, of whom 11 (58%) developed TA-TMA versus 6 of 32 (19%) without infection. Infected patients also showed higher pretreatment sTNFR1 levels (1.93 vs. 1.64 ng/ml, p = 0.0034).

Pretreatment sTNFR1 is a strong early predictor of TA-TMA and mortality in patients with SAA undergoing allo-HSCT, suggesting Tumor Necrosis Factor-alpha-driven inflammation precedes clinical onset. sTNFR1 may be a useful early-warning biomarker, and infection control before transplantation may reduce risk.