Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication following hematopoietic stem cell transplant (HSCT), often resulting in multiorgan dysfunction and requiring PICU-level care. Data on how treatment strategies influence critical illness severity and outcomes in this population remain limited. Methods: We performed a retrospective analysis of pediatric patients (0-22 years) who underwent allogeneic or autologous HSCT at Texas Children’s Hospital and diagnosed with TA-TMA (2011-2024). Diagnosis was made by treating teams; harmonized criteria and high-risk features were applied retrospectively per Schoettler et al., 2023. High-risk disease was defined by ≥1 of the following: rUPCR ≥1 mg/mg, sC5b-9 > ULN, LDH >2× ULN, grade 2–4 GVHD, infection, or organ dysfunction. Patients were grouped by treatment: none, eculizumab, therapeutic plasma exchange (TPE), or both. Outcomes included ICU interventions and survival. Results: Among 110 TA-TMA patients, 41 (37%) required PICU admission. Median age was 8 years; 61% male, 55% Hispanic. Most received allogeneic HSCT (96%) for malignancy (69%) with myeloablative conditioning (89%). Consensus diagnostic criteria were met in 93%; 27% had biopsy-confirmed disease. High-risk features included LDH >2× ULN (94%), proteinuria (40%), and elevated sC5b-9 (39%). Patients treated with both eculizumab and TPE had the highest burden of high-risk features—renal dysfunction (97%, p=0.003), proteinuria (77%, p=0.007), and elevated sC5b-9 (63%, p=0.002)—and required more intensive PICU support: mechanical ventilation (87%, p=0.024), renal replacement therapy (70%, p< 0.001), and prolonged ICU stay (median 36 days, p=0.040). Survival was lowest in those treated with TPE ± eculizumab and highest in those who received no TA-TMA-targeted therapy, likely reflecting baseline severity rather than treatment effect. Conclusions: In pediatric HSCT patients, high-risk TA-TMA features correlate with critical illness severity and resource utilization. Eculizumab and/or TPE were more frequently used in sicker patients, reflecting clinical acuity. Early recognition of high-risk features may support timely interventions. Prospective studies are needed to define optimal treatment timing in this population.
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