Long Term Oral Health Outcomes in the Chronic GVHD Consortium

摘要： 近50%的异基因造血细胞移植受者（AlloHCT）将发展为慢性移植物- 抗宿主病（cGVHD）。口腔受累见于约80%的cGVHD患者。它 表现为粘膜病变，类似扁平苔藓、唾液分泌减少和牙关紧闭。低水平证据表明 口腔cGVHD与牙齿、牙周和粘膜疾病的风险增加有关。当前 cGVHD的口腔健康指南主要基于专家意见。几乎没有证据可以指导治疗 决策或个性化管理计划。 本申请的短期目标是填补上述知识方面的重要空白 并为建立以证据为基础的方法管理口腔癌患者提供依据。 cGVHD。我们的假设是，暴露于口腔cGVHD导致牙齿脱落增加， cGVHD降低了口腔健康相关的生活质量（OHRQL）（次要终点），这是我们 假设是由粘膜敏感性、唾液流量减少和牙关紧闭介导的。我们将继续利用 弗雷德哈钦森癌症研究中心（FHCRC）和丹娜-法伯癌症研究中心（Dana-Farber Cancer Research Center） 研究所（DFCI），NIH资助的cGVHD联盟的两个关键网站，并将我们的研究嵌套在一个大型的 建立基于人口的队列。 首先，我们将确定AlloHCT受者的牙齿脱落率和OHRQL，并探讨其与 口服cGVHD。慢性GVHD联盟的已建立和代表性队列中的受试者将被 在回顾性队列中招募。他们将接受一名经过校准的考官的口试。牙齿脱落 将通过比较当前状态与AlloHCT前口腔检查时收集的数据进行评估。OHRQL 将通过经验证的工具（OHIP 14）进行测量。当前和既往口服cGVHD状态（根据NIH标准） 将通过粘膜检查和联合会数据进行评估。我们将测试 暴露于cGVHD（口服cGVHD的就诊次数）、牙齿脱落和OHRQL之间的关系。次要分析 将评估与牙齿脱落和OHRQL降低相关的其他风险因素。 第二，我们将评估复发性口腔cGVHD和OHRQL之间的关联。既往受试者 （暴露）和当前口服cGVHD的受试者将入组前瞻性队列，并每年重新评估两次，如 目标1。他们将接受全面的口腔检查，包括粘膜和牙周健康，龋齿， 牙齿脱落。将使用经确认的工具测量患者报告的结局。此外，信息将 从每个受试者的初级牙医处收集，包括就诊次数、牙科手术、口腔卫生 说明书、氟化物补充剂和使用促涎剂/唾液替代品。我们将探讨 OHRQL和cGVHD之间的关联，预期口腔cGVHD的存在和强度是 与较低的OHRQL相关。次要分析将评估其他中介因素。

Abstract: Nearly 50% of allogeneic hematopoietic cell transplantation recipients (AlloHCT) will develop chronic graft- versus-host disease (cGVHD). Oral involvement is seen in approximately 80% of patients with cGVHD. It presents as mucosal lesions mimicking lichen planus, hyposalivation, and trismus. Low-level evidence suggests that oral cGVHD is associated with increased risk for dental, periodontal, and mucosal diseases. The current oral health guidelines for cGVHD are largely based on expert opinion. Little evidence exists to guide treatment decisions or to personalize management plans. The short-term objective of this application is to address the important gaps of knowledge described above and generate a rationale for establishing an evidence-based approach in the management of patients with oral cGVHD. Our hypothesis is that exposure to oral cGVHD leads to increased tooth loss and that recalcitrant oral cGVHD decreases oral-health-related quality of life (OHRQL) (secondary endpoint), an effect which we hypothesize is mediated by mucosal sensitivity, reduced salivary flow, and trismus. We will utilize the on-going collaboration between the Fred Hutchinson Cancer Research Center (FHCRC) and the Dana-Farber Cancer Institute (DFCI), two key sites of the NIH-funded cGVHD Consortium and nest our studies in a large established population-based cohort. First, we will determine tooth loss rates and OHRQL in AlloHCT recipients and explore their association with oral cGVHD. Subjects in an established and representative cohort of the Chronic GVHD Consortium will be recruited in a retrospective cohort. They will undergo an oral examination by a calibrated examiner. Tooth loss will be evaluated by comparing current status to data collected at the pre-AlloHCT oral examination. OHRQL will be measured through a validated tool (OHIP14). Current and past oral cGVHD status (per NIH criteria) will be assessed through mucosal examination and through Consortium data. We will test for associations between exposure to cGVHD (number of visits with oral cGVHD), tooth loss, and OHRQL. Secondary analysis will assess other risk factors associated with tooth loss and lower OHRQL. Second, we will evaluate the association between recalcitrant oral cGVHD and OHRQL. Subjects with past (exposed) and current oral cGVHD will be enrolled in a prospective cohort and re-evaluated twice per year as in Aim#1. They will receive a comprehensive oral examination including mucosal and periodontal health, caries, and tooth loss. Patient reported outcomes will be measured with validated tools. Additionally, information will be collected from each subjects' primary dentist including number of visits, dental procedures, oral hygiene instructions, fluoride supplementation, and use of sialogogues/ salivary substitutes. We will explore associations between OHRQL and cGVHD, expecting the presence and intensity of oral cGVHD to be associated with lower OHRQL. Secondary analysis will assess additional mediating factors.