Improving Allogenic Transplant Outcomes in Myeloid Malignancies

项目简介：Bart Scott博士是Fred Hutchinson癌症研究中心（FHCRC）的研究助理，也是华盛顿大学的代理临床讲师。他的长期职业目标是成为一名独立的临床研究者，他的研究兴趣包括改善髓系恶性肿瘤患者的移植结果。职业发展计划是一项综合计划，包括机构会议、流行病学硕士学位、负责任研究方面的继续培训以及咨询委员会的适当评估和反馈。Scott博士进行了一项回顾性分析，比较了骨髓增生异常综合征（MDS）和急性髓性白血病（AML）患者的清髓和非清髓方案的结果，这是该建议的基础。数据表明，这两种方法都有明显的优缺点；只有前瞻性试验才能更明确地解决总生存期的潜在益处。在博士的指导下。Joachim Deeg和Rainer Storb博士设计并将实施一项III期试验，比较MDS和AML患者的清髓和非清髓调节方案的毒性和疗效。Scott博士将是本次试验的首席研究员，主要负责所有方面的工作，包括设计同意和同意表格、获得IRB批准、与外部中心合作、患者累积、审查主要数据的资格、报告严重不良事件、分析和发布数据。具体目标如下：1)确定骨髓清除（环磷酰胺或氟达拉滨和丁硫凡）或非骨髓清除（氟达拉滨和低剂量全身照射）方案治疗的MDS和AML患者的总生存期是否存在差异；2)确定用于移植前“减体积”的化疗对骨髓清除和非骨髓清除后死亡率、复发和移植的影响；3)表征清髓方案中静脉注射丁硫凡的药代动力学（PK），并确定PK参数对移植结果的影响。FHCRC是髓系恶性肿瘤治疗领域的领先机构，为Scott博士发展成为一名独立临床研究者提供了良好的环境，他在开发和管理旨在提高髓系恶性肿瘤患者生存率和生活质量的临床试验方面具有专业知识。相关性：本提案的目标是通过开发更安全、更有效的移植方案来提高白血病及相关疾病患者的生存率和生活质量。

DESCRIPTION (provided by applicant): Project Summary: Dr. Bart Scott is a Research Associate at the Fred Hutchinson Cancer Research Center (FHCRC) and an Acting Clinical Instructor at the University of Washington. His long-term career goal is to be an independent clinical investigator, and his research interests involve improving transplant outcomes in patients with myeloid malignancies. The Career Development Plan is a comprehensive program consisting of institutional meetings, a master's degree in epidemiology, continued training in responsible research, and appropriate evaluation and feedback from an Advisory Committee. Dr. Scott performed a retrospective analysis comparing results with myeloablative and nonmyeloablative regimens in patients with Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML), which serves as the basis for this proposal. The data suggest there are distinct advantages and disadvantages with either approach; only a prospective trial can more definitively address the potential benefits in overall survival. With the mentorship of Drs. Joachim Deeg and Rainer Storb, Dr. Scott has designed and will implement a phase III trial comparing toxicity and efficacy of myeloablative and nonmyeloablative conditioning regimens in patients with MDS and AML. Dr. Scott will be the principal investigator of this trial and will be primarily responsible for all aspects, which include designing consent and assent forms, obtaining IRB approval, collaborating with outside centers, patient accrual, reviewing primary data for eligibility, reporting serious adverse events, and analyzing and publishing data. The specific aims are as follows: 1) determine if there is an overall survival difference in patients with MDS and AML conditioned with myeloablative (cyclophosphamide or fludarabine and busulfan) or nonmyeloablative (fludarabine and low dose total body irradiation) regimens, 2) determine the impact of chemotherapy used for pre-transplant "debulking" on mortality, relapse, and engraftment after myeloablative and nonmyeloablative conditioning, and 3) characterize pharmacokinetics (PK) of intravenous busulfan in the myeloablative regimens, and determine the impact of PK parameters on transplant outcomes. The FHCRC is a leading institution in the treatment of myeloid malignancies and provides an excellent environment to foster the development of Dr. Scott into an independent clinical investigator with expertise in developing and managing clinical trials designed to improve survival and quality of life in patients with myeloid malignancies. Relevance: The goal of this proposal is to improve survival and quality of life in patients with leukemia and related diseases by developing safer and more effective transplant options.