ALLOGENIC BLOOD AND MARROW TRANSPLANT FOR ACUTE MYELOGENOUS LEUKEMIA

急性髓性白血病的同种异体血液和骨髓移植

• 批准号: 6338685
• 负责人: RICHARD E. CHAMPLIN
• 金额: $ 16.32万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-04 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338685
• 关键词: acute myelogenous leukemia; apoptosis; bone marrow transplantation; clinical research; colony stimulating factor; combination cancer therapy; graft versus host disease; hematopoietic stem cells; hematopoietic tissue transplantation; homologous transplantation; human subject; human therapy evaluation; major histocompatibility complex; neoplasm /cancer chemotherapy; neoplasm /cancer remission /regression; retinoate; thymidine kinase

High dose chemoradiotherapy with allogeneic hematopoietic transplantation is an effective treatment for AML. This approach was conceived as a strategy to produce marrow ablation, but recent data indicates that the immune mediated graft-vs-leukemia effect is also important. Relapse of leukemia remains a major problem. In this project we evaluate a number of innovative approaches designed to improve the outcome of allogeneic transplantation. This includes evaluation of decitabine as a novel agent for preparative regimens with allogeneic peripheral blood progenitor cell transplants in matched siblings. The recent promising results with donor lymphocyte infusions suggests that achieving engraftment of donor peripheral blood cells after standard dose chemotherapy for induction of graft-vs-leukemia might also be beneficial. This will be studied in older patients who have a matched sibling donor with primary endpoints of analysis being engraftment, GVHD and remission duration. Allogeneic transplants have been less successful in adult patients who lack an HLA identical sibling; we examine two innovative approaches to achieve engraftment without GVHD in this setting. Prevention of GVHD in patients receiving allogeneic transplant will be studied using thymidine kinase transduced donor lymphocytes (suicidal lymphocytes) which can be ablate by ganciclovir treatment. For mismatched related donor transplants we are evaluating CD34 selected marrow plus peripheral blood progenitors, providing a large progenitor cell dose and depleted of aIloreactive T-cells. For unrelated donor or mismatched transplants, we will study an innovative T-cell depletion method, using a system to retain graft facilitating cells to enhance engraftment while still preventing GVHD. For patients who relapse, we reported the unique observation that G-CSF treatment can reinduce remissions; we further examine the efficacy of this approach and attempt to define its mechanism. We also will study whether retinoic acid which downregulates bcl-2 and enhances apoptosis, will enhance the therapeutic effect. Lastly we will examine the presence of minimal residual AML in patients after transplantation therapies. This project interacts extensively with the other clinical projects within this proposal.

高剂量放化疗联合同种异体造血 移植是治疗 AML 的有效方法。这种做法 被认为是一种产生骨髓消融的策略，但最近 数据表明，免疫介导的移植物抗白血病效应 也很重要。白血病复发仍然是一个主要问题。在 这个项目我们评估了一些创新方法 旨在改善同种异体移植的结果。 这包括对地西他滨作为新药的评估 同种异体外周血祖细胞的制备方案 对匹配的兄弟姐妹进行细胞移植。最近有希望的结果 供体淋巴细胞输注表明实现 标准剂量后供体外周血细胞的植入 诱导移植物抗白血病的化疗也可能是 有利。这将在患有以下疾病的老年患者中进行研究： 匹配的兄弟姐妹捐赠者的主要分析终点是 植入、GVHD 和缓解持续时间。同种异体移植 在缺乏 HLA 的成年患者中不太成功 同父异母的兄弟姐妹；我们研究了两种创新方法来实现 在这种情况下，无需进行 GVHD 移植。预防GVHD 接受同种异体移植的患者将使用 胸苷激酶转导的供体淋巴细胞（自杀性 淋巴细胞），可以通过更昔洛韦治疗消除。为了 我们正在评估 CD34 不匹配的相关供体移植 选择的骨髓加上外周血祖细胞，提供 大剂量祖细胞并耗尽异反应性 T 细胞。 对于不相关的供体或不匹配的移植物，我们将研究 创新的 T 细胞去除方法，使用保留移植物的系统 促进细胞增强植入，同时仍然防止 移植物抗宿主病。对于复发的患者，我们报告了独特的观察结果 G-CSF 治疗可以重新诱导缓解；我们进一步检查 这种方法的功效并试图定义其机制。 我们还将研究视黄酸是否会下调 bcl-2 并增强细胞凋亡，会增强治疗效果。 最后，我们将检查患者中是否存在微小残留 AML。 移植治疗后的患者。该项目交互 与该提案中的其他临床项目广泛合作。