CELLULAR IMMUNOTHERAPY FOR HEMATOLOGIC MALIGNANCY

描述：(申请人描述)这是一份申请K23的申请书 获奖。候选人约翰·莱文博士是一名初级教员， 加州大学血液和骨髓干细胞移植项目 密歇根州。莱文博士的长期目标是在 血液病的细胞免疫治疗。莱文博士的研究 该项目将侧重于过继细胞免疫疗法的潜在作用 防止异基因干细胞移植后复发。不幸的是， 传统清髓性异基因干细胞移植在许多情况下失败 高危患者，特别是那些年龄较大或患有较晚期疾病的患者 白血病。患有疾病的高危患者，如晚期CML或 复发性或难治性急性白血病，两到三年无病 同胞异基因造血干细胞移植后的存活率在0-29%之间。治疗失败的原因是 通常是由于与方案相关的毒性、移植物抗宿主病或复发。候选人 提出了一种低强度条件性移植的策略 预防性过继免疫疗法作为预防复发的一种手段 GVL，同时将GVHD或方案相关毒性的风险降至最低。莱文博士 将由詹姆斯博士组成的咨询委员会积极指导 费拉拉，血液和骨髓干细胞移植主任，沃拉维特博士 Ratanatharathorn博士和UMCC生物统计核心主任Jeremy Taylor博士。 从低强度调节的基本策略开始，然后是 预防性过继免疫治疗，患者样本将 前瞻性收集和分析白血病和血吸虫病宿主标志物 毒性。从前瞻性收集和分析中获得的信息 将用于确定治疗失败的原因，当 它会发生，因此可能有助于设计未来的治疗方法。 旨在提高无复发存活率和减少治疗的策略- 相关毒性，尤其是移植物抗宿主病。其中一个特别重要的方面 项目是该方法将根据临床情况进行调整 复发和移植物抗宿主病的观察及其实验室相关性。这个 具体目标是： 1.进行预防性细胞免疫治疗的I-II期试验 低强度条件化异基因造血干细胞治疗 用于高危血液系统恶性肿瘤。 2a.评估一组细胞因子作为GVHD和GVHD替代标志物的作用 将这些与上述试验期间的临床结果相关联。 2B。将微小残留病的变化与临床结果相关联 在上述审判期间。

DESCRIPTION: (Applicant's Description) This is an application for a K23 award. The candidate, Dr. John Levine, is a junior faculty member in the Blood and Marrow Stem Cell Transplantation Program at the University of Michigan. Dr. Levine's long-term goal is to conduct clinical research in cellular immunotherapy for hematologic disorders. Dr. Levine's research project will focus on the potential role of adoptive cellular immunotherapy to prevent relapse after allogeneic stem cell transplantation. Unfortunately, conventional myeloablative allogeneic stem cell transplantation fails in many high-risk patients, particularly those who are older or have more advanced leukemia. In high-risk patients with diseases such as advanced CML or multiply relapsed or refractory acute leukemia, two to three year disease-free survival after sibling HSCT ranges from 0-29 percent. Treatment failures are often due to regimen-related toxicity, GVHD, or relapse. The candidate proposes a strategy of a low intensity conditioned transplant followed by prophylactic adoptive immunotherapy as a means of preventing relapse through GVL while minimizing risk of GVHD or regimen-related toxicity. Dr. Levine will be actively mentored by an advisory committee consisting of Dr. James Ferrara, Director of Blood and Marrow Stem Cell Transplantation, Dr. Voravit Ratanatharathorn, and Dr. Jeremy Taylor, Director of UMCC Biostatistics Core. Starting with a basic strategy of low intensity conditioning followed by prophylactic adoptive immunotherapy, samples from patients will be prospectively collected and analyzed for both leukemia and host markers of toxicity. The information gained from the prospective collection and analysis of these samples will be used to determine reasons for treatment failure, when it occurs, and thus may be helpful in the design of future treatment strategies intended to increase relapse-free survival and decrease treatment- related toxicity, especially GVHD. An especially important aspect to this project is that the approach will be adjusted based on both clinical observations of relapse and GVHD and their laboratory correlates. The specific aims are: 1. To conduct a phase I-II trial of prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. 2A. To evaluate a panel of cytokines as surrogate markers for GVHD and correlate these with clinical outcomes during the above trial. 2B. To correlate changes in minimal residual disease with clinical outcomes during the above trial.