Improving Allogenic Transplant Outcomes in Myeloid Malignancies

描述（由申请人提供）：项目摘要：巴特斯科特博士是弗雷德哈钦森癌症研究中心（FHCRC）的研究助理和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骨髓恶性肿瘤患者的移植结果。职业发展计划是一个综合方案，包括机构会议、流行病学硕士学位、负责研究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）患者的清髓性和非清髓性方案的结果，这是本提案的基础。数据表明，这两种方法都有明显的优点和缺点;只有前瞻性试验才能更明确地说明总生存率的潜在益处。在Joachim Deeg和Rainer Storb博士的指导下，Scott博士设计并将实施一项III期试验，比较MDS和AML患者清髓性和非清髓性预处理方案的毒性和疗效。Scott博士将是本试验的主要研究者，主要负责所有方面，包括设计知情同意书和同意书、获得IRB批准、与外部中心合作、患者招募、审查合格性的主要数据、报告严重不良事件以及分析和发布数据。具体目标如下：1）确定在以清髓性治疗为条件的MDS和AML患者中是否存在总体存活差异，（环磷酰胺或氟达拉滨和白消安）或非清髓性（氟达拉滨和低剂量全身照射）方案，2）确定用于移植前“减积”的化疗对清髓性和非清髓性预处理后的死亡率、复发和植入的影响，和3）描述清髓方案中静脉内白消安的药代动力学（PK），并确定PK参数对移植结果的影响。FHCRC是治疗骨髓恶性肿瘤的领先机构，并提供了一个良好的环境，以促进Scott博士发展成为一名独立的临床研究者，具有开发和管理旨在改善骨髓恶性肿瘤患者生存和生活质量的临床试验的专业知识。相关性：该提案的目标是通过开发更安全，更有效的移植选择来提高白血病和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.