CELLULAR IMMUNOTHERAPY FOR HEMATOLOGIC MALIGNANCY

描述：（申请人的描述）这是一个K23的应用程序 奖 候选人，约翰莱文博士，是一个初级教员在 血液和骨髓干细胞移植项目 密歇根 莱文博士的长期目标是进行临床研究， 用于血液病的细胞免疫疗法。 莱文博士的研究 该项目将重点关注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， 传统的清髓性异基因干细胞移植在许多情况下都失败了 高风险患者，尤其是年龄较大或患有更严重疾病的患者 白血病 在患有疾病的高危患者中，如晚期CML或 多次复发或难治性急性白血病，2 - 3年无病 同胞HSCT后的存活率为0- 29%。 治疗失败是 通常是由于方案相关毒性、GVHD或复发。 候选 提出了一种低强度条件移植的策略， 预防性过继免疫治疗作为预防复发的手段， GVL，同时最大限度地减少GVHD或方案相关毒性的风险。 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，Voravit博士 Ratanatharathorn和UMCC生物统计核心主任Jeremy Taylor博士。 从低强度条件反射的基本策略开始， 预防性过继免疫治疗，患者的样本将 前瞻性收集并分析白血病和宿主标志物， 毒性 从前瞻性收集和分析中获得的信息 将使用这些样本中的10%确定治疗失败的原因， 它发生，因此可能有助于未来治疗的设计 旨在提高无复发生存率和减少治疗的策略- 相关毒性，尤其是GVHD。 一个特别重要的方面是 该项目是，该方法将根据两个临床 观察复发和GVHD及其实验室相关性。 的 具体目标是： 1. 进行预防性细胞免疫治疗的I-II期试验， 使用低强度预处理的异基因造血干细胞治疗 高危恶性血液病的治疗 2A. 评价一组细胞因子作为GVHD的替代标志物， 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局相关联 在上述审判中。

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.