Eculizumab for Pediatric Hematopoietic Cell Transplant-Associated Thrombotic Microangiopathy: Real-World Response Rates, Predictors of Poor Response, and an Optimal Time Point for Treatment Response Assessment.

BACKGROUND

Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic cell transplantation (HCT) associated with high morbidity and mortality. The disease is driven by endothelial injury and complement dysregulation. Eculizumab, a complement C5 inhibitor, has been used off-label for TA-TMA, but reported outcomes are variable. Real-world response rates and predictors of treatment failure remain incompletely defined, particularly in children. Additionally, the optimal time point to assess treatment response has been identified as a key gap in the field.

OBJECTIVE

To evaluate real-world response rates, predictors of nonresponse, and clinical outcomes among children treated with eculizumab for TA-TMA, and to identify an optimal time point for response assessment.

METHODS

This retrospective study serially enrolled all patients treated with eculizumab for TA-TMA across 7 centers from 2015 to 2023. Organ, hematologic, and overall responses were defined using Consensus criteria as complete response (CR), clinically meaningful partial response (PR), or no response (NR). Clinical characteristics, treatment patterns, and outcomes were analyzed. Multivariable models were used to identify predictors of NR and mortality.

RESULTS

Among 176 patients, 74% were allogeneic HCT recipients, 42% of whom had grade 3 to 4 acute graft-versus-host disease (GVHD). The cohort was enriched for severe disease, with 96% experiencing ≥1 organ dysfunction and 61.4% requiring intensive care. TA-TMA was diagnosed at a median of 49 days post-HCT. Patients received a median of 12 doses of eculizumab over a median duration of 10 weeks. Six months from treatment initiation, 24% achieved an overall CR, 19% achieved PR, and 57% had NR. Response rates were similar across high-risk subgroups defined by the Jodele criteria, Consensus criteria, and among allogeneic recipients with ≥1 organ dysfunction. Six-month nonrelapse mortality (NRM) was significantly lower among responders (CR/PR) compared with nonresponders (2.3% vs. 24.2%). Allogeneic HCT recipients were more likely to have NR than autologous recipients (HR, 1.84). Multiorgan dysfunction at TA-TMA diagnosis was independently associated with NR across transplant types. Patients who did not achieve at least a PR by day 45 had ≤25% likelihood of subsequent response and a 3.74-fold higher mortality risk compared with those with PR/CR at day 45.

CONCLUSIONS

In this large pediatric cohort, approximately half of children with TA-TMA demonstrated clinical improvement after treatment with eculizumab, whereas the remaining half had no response and substantially worse survival. Multiorgan dysfunction was an adjusted risk factor for poor response across transplant types. Failure to achieve at least a partial response by day 45 strongly predicts poor response and is associated with an increased mortality risk, supporting this as a clinically meaningful time point to reassess therapy and consider alternative treatment strategies. © 2026 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.