Conversion from calcineurin inhibitor to ruxolitinib as GVHD prophylaxis during patients with transplant-associated thrombotic microangiopathy.

Authors

Yan Zhang, Hanyin Liang, Zhiping Fan, Huiqing He, Zhi Liu, Fen Huang, Li Xuan, Ren Lin, Xiaofang Li, Jing Sun, Qifa Liu, Na Xu

Published in

Transplantation and cellular therapy. Sep 16, 2026. Epub Sep 16, 2026.

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with multifactorial etiology. Existing clinical guidelines recommend discontinuation or tapering of calcineurin inhibitors (CNIs) as the primary intervention after the initial TMA diagnosis; however, data on the options for immunosuppression manipulation (ISM) are limited. Ruxolitinib is an effective option in treatment of steroid refractory graft-versus-host disease (SR-GVHD), which seems promising to replace CNIs as a prophylactic agent with better GVHD control in patients with TA-TMA.
We retrospectively analyzed the outcomes of 48 TA-TMA patients who received ISM with steroids (steroid group) or ruxolitinib (ruxolitinib group) as CNI substitutes.
The primary endpoint was not met: the ORR at 4 weeks did not differ significantly between the ruxolitinib and steroid groups (65.2% vs. 80.0%, P = 0.250). However, in exploratory secondary analyses, more patients in the ruxolitinib group achieved complete response (CR) than in the steroid group (40% vs. 13%, P=0.036), and first remission was achieved more rapidly (13.5 vs. 25 days, P=0.046). Additionally, the ruxolitinib group demonstrated faster normalization of lactate dehydrogenase (LDH) levels and significantly better overall survival (HR 0.32, 95% CI 0.12-0.84, p=0.025) and relapse-free survival (HR 0.41, 95% CI 0.17-0.99, p=0.048) than the steroid group. Although hematologic recovery was slower in the ruxolitinib group than in the steroid group, we attribute this to ruxolitinib-induced myelosuppression. Infection was a significant risk factor in the ruxolitinib group (P=0.0426). However, there were no significant differences in the incidence of infection following treatment with steroid or ruxolitinib: pneumonia (26.1% vs. 16%, P=0.487), sepsis (17.4% vs. 12%, P=0.696), Epstein-Barr virus (EBV) reactivation (47.8% vs. 36%, P=0.406), or Cytomegalovirus (CMV) reactivation (56.5% vs. 52%, P=0.753).
In this pilot study, the primary endpoint (ORR) was not met. Exploratory secondary analyses suggest that replacing CNIs with ruxolitinib during TA-TMA is feasible and may be associated with more rapid LDH normalization and CR, at the cost of slower peripheral count recovery; these observations are hypothesis-generating and require confirmation in adequately powered, prospective, multicenter studies.

PMID:
42749189
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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