Chronic graft-versus-host disease

这一努力仍然非常富有成效，与GVHD相关的年度出版物产量证明了这一点，包括该分支发起的伊马替尼临床试验的出版物（见下文）。此外，我还对cGVHD的新皮肤表现的鉴定做出了几项重要贡献，并确定了全身照射是cGVHD的危险因素。即将出版的一份报告描述了皮肤GVHD的自身免疫性皮肤表现以及与女性造血细胞供体的联系。此外，这个小组已经发展了全国声誉作为一个具有挑战性的案件的转诊中心，从全国各地进行评估。甲磺酸伊马替尼是一种酪氨酸激酶抑制剂，专门用于抑制参与BCR-ABL信号转导的蛋白质的酪氨酸磷酸化。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，这些信号通路是与纤维形成过程密切相关的细胞因子。该试验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多学科项目中进行治疗和评估。在评估具有多样化患者群体的极其复杂的疾病时，cGVHD临床试验的进入标准和反应评估标准缺乏标准化。这导致了临床试验数据解释的困难。诊断和反应评估基于美国国立卫生研究院慢性移植物抗宿主病临床试验标准共识发展项目，重点关注明确定义的cGVHD器官表现，明确定义的进入、同步治疗和评估标准。到目前为止，所有患者都达到了试验的主要终点（6个月），目前正在收集实验室和其他研究数据，准备最终稿件。

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.