ArticleExperimental and therapeutic medicine2026
Mammalian target of rapamycin inhibitors as the treatment for steroid-refractory acute graft-vs.-host disease after allogeneic hematopoietic stem cell transplantation: A systematic review and individual patient data meta-analysis.
Article in Experimental and therapeutic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The prognosis of patients with steroid-refractory acute graft-vs.-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains poor. Furthermore, the recommendations for second- and third-line therapeutic approaches are controversial. The present study aimed to analyze the efficacy and safety of mammalian target of rapamycin (mTOR) inhibitors in SR-aGVHD after allo-HSCT. The present study searched the PubMed and Embase databases for relevant publications from December 2001 to September 2024. The primary endpoints were overall response rate (ORR), complete response rate (CRR), chronic GVHD, overall survival (OS) and infection-related complications at any time after mTOR inhibitor therapy. The response rate at 1 month after mTOR inhibitor therapy was also assessed. The present meta-analysis included 5 studies involving 134 patients. The ORR and CRR at any time were 65% (95% CI, 44-81%) and 46% (95% CI, 22-72%) after mTOR inhibitor-based therapy for SR-aGVHD, respectively, with 1- to 3-year OS rate ranging from 36% (95% CI, 27-46%) to 30% (95% CI, 20-42%) The ORR and CRR after a 1-month treatment with mTOR inhibitors were 57% (95% CI, 34-78%) and 58% (95% CI, 13-93%), respectively. Transplant-associated thrombotic microangiopathy (TA-TMA) and cytopenia occurred in 36% (95% CI, 22-52%) and 43% (95% CI, 18-72%) of patients with SR-aGVHD, leading to treatment interruption with mTOR inhibitors in 10% (95% CI, 5-22%) and in 6% (95% CI, 2-13%) of patients, respectively. The highest CRR (78%) was observed in steroid-refractory patients treated with mTOR inhibitors combined with IL-2R antagonists, with an mTOR inhibitor serum trough level of 7-13 ng/ml, although a minimum therapeutic level was 4 ng/ml. Prolonged therapy was more likely to be effective. In conclusion, mTOR inhibitors exhibit potent activity against SR-aGVHD. However, their use may be associated with complications such as TA-TMA and cytopenia.
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