{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T01:25:10Z","timestamp":1768699510359,"version":"3.49.0"},"reference-count":48,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"abstract":"<jats:p>Introduction: Steroid-refractory cGVHD (SR-cGVHD) presents new great challenges for treatment. We have reported that imatinib monotherapy was effective to SR-cGVHD, but the CR rate was not satisfactory and the benefit was not showed specific to some target organs, previously. Imatinib and statin drugs have been recognized to regulate T-cell function, statins also have been demonstrated endothelia protection, but whether this combination therapy was able to improve the efficacy remains unknown. Therefore, we designed this prospective, single-arm, open-label trial to investigate the efficacy of imatinib-based combination therapy in the treatment of SR-cGVHD for the first time. Methods: Sixty SR-cGVHD patients were entered into this trial to investigate the combination of imatinib mesylate and atorvastatin calcium for the treatment of SR-cGVHD. The primary endpoint included the overall response rate (ORR) after 6 months of combined treatment. The secondary endpoints included an evaluation of survival, changes in T-cell subsets, and adverse events. Results: At baseline, 45% (27\/60) of patients had moderate cGVHD, and 55.0% (33\/60) of patients had severe cGVHD. At the 6-month follow-up, a clinical response was achieved in 70.0% of patients, and a complete response (CR) was achieved in 26.7%. A total of 11.7% (7\/60) of patients stopped immunosuppressive therapy at this point. After 6 months of treatment, the ORR rates of the liver, skin, eyes, and oral cavity were 80.6%, 78.1%, 61.5%, and 60.9%, respectively, with the liver also having the highest CR of 58.1%. The patients with moderate cGVHD had a better CR rate than those with severe cGVHD (55.6% vs. 3.0%, p &amp;lt; 0.0001). The overall survival in patients with ORR was improved (p = 0.0106). Lung involvement is an independent risk factor to affected ORR achievement (p = 0.021, HR = 0.335, 95% CI: 0.133\u20130.847), and the dosage of steroids was reduced in ORR patients. In clinical response patients, the ratio of CD8+ T cells (p = 0.0117) and Th17 cells (p = 0.0171) decreased, while the number of Treg cells (p = 0.0147) increased after 3 months. The most common adverse events were edema, nausea, and neutropenia, which were 13.3%, 11.7%, and 11.7%, respectively. Conclusion: Combination treatment with imatinib mesylate and atorvastatin calcium was effective in treating SR-cGVHD and significantly decreased target organ injury, especially liver damage, indicating that T-cell regulatory function may play an important role in this process. <\/jats:p>","DOI":"10.1159\/000536174","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T22:01:05Z","timestamp":1708120865000},"page":"499-510","source":"Crossref","is-referenced-by-count":1,"title":["Efficiency and Toxicity of Imatinib Mesylate Combined with Atorvastatin Calcium in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease: A Single-Center, Prospective, Single-Arm, Open-Label 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