Molés-Poveda P, Montesinos P, Sanz-Caballer J, de Unamuno B, Piñana J L, Sahuquillo A, Botella-Estrada R
Unidad de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España; Instituto de Investigación Sanitaria La Fe, Valencia, España.
Unidad de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España.
Actas Dermosifiliogr (Engl Ed). 2018 Apr;109(3):241-247. doi: 10.1016/j.ad.2017.11.003. Epub 2017 Dec 15.
Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor.
To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib.
Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible.
In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months).
This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.
慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植后晚期非复发死亡的最重要原因。硬皮病样cGVHD通常对类固醇耐药，仍然是一个治疗挑战。在硬皮病样cGVHD患者中已报道存在针对血小板衍生生长因子受体（PDGFR）的激活抗体。这些抗体诱导PDGFR磷酸化并导致纤维化。越来越多的证据表明，酪氨酸激酶抑制剂伊马替尼成功治疗硬皮病样cGVHD。
评估伊马替尼对皮肤硬皮病样cGVHD的疗效。
对单中心18例对免疫抑制剂耐药的硬皮病样cGVHD患者进行回顾性研究，这些患者接受了伊马替尼治疗。在开始使用伊马替尼后的1、3、6、9、12和18个月，由临床医生评估和患者主观反应来评价治疗反应。反应分为完全缓解、部分缓解、显著缓解、无变化或进展。逐渐停用类固醇的情况分为完全停用、部分停用或无法停用。
在我们的研究系列中，4例（22%）患者达到完全缓解，9例（50%）患者部分缓解，2例（11%）患者显著缓解，2例（11%）患者无变化，1例（6%）患者在最后随访时有疾病进展。从开始使用伊马替尼到出现任何程度反应的平均时间为2.75个月（范围1 - 9个月）。
本研究进一步证明了伊马替尼在治疗类固醇耐药的硬皮病样cGVHD中的作用。
