Chronic graft-versus-host disease

这一努力继续卓有成效，与GVHD有关的年度出版物产出，包括科发起的伊马替尼临床试验(见下文)的出版就证明了这一点。此外，我在cGVHD新的皮肤表现的识别方面做出了一些重要贡献，以及确认全身照射作为cGVHD的危险因素所起的作用。一篇报道描述了皮肤移植物抗宿主病的自身免疫性皮肤表现，以及与女性造血细胞供者的联系。此外，该组织还建立了全国声誉，成为从全国各地接受评估的具有挑战性的案例的转介中心。甲磺酸伊马替尼是一种酪氨酸激酶抑制剂，专为抑制参与bcr-abl信号转导的蛋白质的酪氨酸磷酸化而开发。此外，它还对血小板衍生生长因子(PDGF)和转化生长因子(TGF)信号通路具有高度的特异性和生物活性，这两种细胞因子在纤维化过程中起着重要的作用。这项试验中的患者在全国范围内招募，并在国家癌症研究所/国家卫生研究院的cGVHD多学科计划中进行治疗和评估。在评估一种具有不同患者群体的极其复杂的疾病时，cGVHD临床试验存在入选和反应评估标准标准化较差的问题。这给临床试验数据的解释带来了困难。诊断和反应评估基于美国国立卫生研究院关于慢性移植物抗宿主病临床试验标准的共识发展项目，重点放在明确定义的cGVHD器官表现上，包括明确定义的条目、同时治疗和评估标准。到目前为止，所有患者都达到了试验的主要结果(6个月)终点，目前将收集实验室和其他研究研究数据，以准备最终手稿。

This effort continues to be very productive as evidenced by the yearly publication output related to GVHD, inclugin publication of the Branch initiated imatinib clinical trial (see below). In addition, I have made several important contributions to the identification of novel skin manifestations of cGVHD, as well as identified the role of total body irradiation as a risk factor for cGVHD. In press is a report describing autoimmune skin manifestations of cutaneous GVHD and a link to female hematopoeitic cell donor. In addition, this group has developed a national reputation as a referral center for challenging cases to be evaluated from around the country. Imatinib mesylate is a tyrosine kinase inhibitor that was specifically developed to target inhibition of tyrosine phosphorylation of proteins involved in BCR-ABL signal transduction. It additionally has a high degree of specificity and biological activity against both platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) signaling pathways, cytokines strongly implicated in the fibrogenesis process. Patients in this trial were recruited nationwide and treated and evaluated in the cGVHD Multidisciplinary Program at the National Cancer Institute/National Institutes of Health. In evaluating an exceedingly complex disease with a diverse patient population, cGVHD clinical trials suffer from poor standardization of entry and response-assessment criteria. This has resulted in difficulties in clinical trial data interpretation. Diagnosis and response assessment are based on the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease criteria and is focused on well-defined cGVHD organ manifestations with clearly defined entry, concurrent treatment, and evaluation criteria. To date all patients have met the primary outcome (6 month) endpoint of the trial and will are currently collecting the laboratory and other research study data in preparion of a final manuscript.