Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a multifactorial etiology. Existing clinical guidelines recommend discontinuation or tapering of calcineurin inhibitors (CNI) as the primary intervention after initial TMA diagnosis, however, there are limited data on the options for immunosuppression manipulation (ISM). Ruxolitinib is an effective option in treatment of steroid refractory graft-versus-host disease (SR-GVHD), which seems promising to replace CNI as a prophylactic agent with better GVHD control during patients with TA-TMA.

Methods: In our study we retrospectively analyzed outcomes of 48 patients with TA-TMA with ISM and substitution either with steroids (steroid group) or ruxolitinib (ruxolitinib group).

Results: The overall response rate (ORR) was no significant in the ruxolitinib group compared to steroids group (65.2% vs 80%, P=0.250). However, more patients in the ruxolitinib group achieved complete response（CR）compared to the steroids group (13% vs. 40%, P=0.036), and the remission was achieved more rapidly (13.5 days vs. 25 days, P=0.046) in ruxolitinib group. Ruxolitinib group with faster time to normalization of LDH, significantly better 1-year overall survival (HR 0.32, 95%CI 0.12-0.84, p=0.025), 1-year relapse-free survival (HR 0.41, 95%CI 0.17-0.99, p=0.048). Infections were found to be a significant risk factor in ruxolitinib group (p=0.0426). There were no significant differences in incidence of infections between steroid and ruxolitinib groups: pneumonia (26.1% vs. 16%, P=0.487), sepsis (17.4% vs. 12%, P=0.696), EBV (47.8% vs. 36%, P=0.406) and CMV (56.5% vs. 52%, P=0.753) reactivation.

Conclusion: Replacement of CNIs with ruxolitinib in patients with TA-TMA might be an acceptable alternative, and a multicenter confirmatory study of CNIs replacement with ruxolitinib is justified.

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2025
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