Department of Clinical Hematology, Catalan Institute of Oncology, Hospital Duran i Reynals, Av. Gran Vía No. 199-203, Hospitalet de Llobregat, Barcelona, Spain
Biol Blood Marrow Transplant. 2012 Feb;18(2):318-23. doi: 10.1016/j.bbmt.2011.10.042. Epub 2011 Nov 7.
Sclerotic chronic graft-versus-host disease (scGVHD) is a severe form of this disease that resembles systemic sclerosis and has limited and disappointing treatment options. Tyrosine kinase inhibitors (TKI) targeting up-regulated profibrotic pathways, such as imatinib mesylate, have been proposed as a potential therapeutic approach for patients with scGVHD. Dasatinib, a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects. We present here the first direct clinical evidence, from 3 patients treated in a small single-center series, suggesting that dasatinib can be a therapeutic option for patients with severe scGVHD resistant or intolerant to imatinib. All patients achieved partial response, with improvement in scGHVD target organs severity, joint mobility, lung impairment, and deep fibrotic lesions. This clinical response has remained stable or continued to improve after a median of 22 months (20-25) on dasatinib treatment, with very good tolerance. In addition, corticosteroids could be discontinued or significantly reduced in all patients. This clinical evidence suggests that dasatinib could be a safe and effective alternative for scGVHD patients refractory to corticosteroids and resistant or intolerant to imatinib. Based on these preliminary findings, and in order to address appropriate patient selection, time of intervention, and choice of drug, future larger studies should more formally establish the efficacy and safety of second-generation TKI for the treatment of scGVHD.
硬化性慢性移植物抗宿主病（scGVHD）是一种严重的疾病形式，类似于系统性硬化症，且治疗选择有限，效果不佳。针对上调的致纤维化途径的酪氨酸激酶抑制剂（TKI），如甲磺酸伊马替尼，已被提议作为 scGVHD 患者的潜在治疗方法。达沙替尼是第二代 TKI，在对伊马替尼耐药或不耐受的慢性髓性白血病患者中具有良好的安全性和疗效，也显示出强大的抗纤维化作用。我们在此介绍了来自 3 名在小型单中心系列中接受治疗的患者的首个直接临床证据，表明达沙替尼可能是对伊马替尼耐药或不耐受的严重 scGVHD 患者的一种治疗选择。所有患者均获得部分缓解，scGHVD 靶器官严重程度、关节活动度、肺损伤和深部纤维化病变均得到改善。在接受达沙替尼治疗中位 22 个月（20-25）后，这种临床反应保持稳定或继续改善，且耐受性非常好。此外，所有患者的皮质类固醇均能停用或显著减少。这些临床证据表明，达沙替尼可能是对皮质类固醇耐药且对伊马替尼耐药或不耐受的 scGVHD 患者的安全有效的替代治疗方法。基于这些初步发现，为了确定适当的患者选择、干预时间和药物选择，未来的更大规模研究应更正式地确定第二代 TKI 治疗 scGVHD 的疗效和安全性。
