ALLOGENIC BLOOD AND MARROW TRANSPLANT FOR ACUTE MYELOGENOUS LEUKEMIA

大剂量异基因造血放化疗 移植是治疗急性髓系白血病的有效方法。这种方法 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……里面 在这个项目中，我们评估了一些创新方法 旨在改善同种异体移植的结果。 这包括评估地西他滨作为一种新的药物治疗 异基因外周血祖细胞制备方案的研究 在匹配的兄弟姐妹中进行细胞移植。最近有希望的结果 捐献者淋巴细胞的输注表明 供者外周血细胞在标准剂量后的植入 诱导移植物抗白血病的化疗也可能是 有益的。这将在老年患者中进行研究。 匹配的兄弟姐妹供体，主要分析终点为 植入、移植物抗宿主病和缓解期。同种异体移植 在缺乏人类白细胞抗原的成年患者中不太成功 相同的兄弟姐妹；我们研究了两种创新的方法来实现 在此设置中不使用GVHD进行植片。儿童移植物抗宿主病的预防 接受同种异体移植的患者将使用 胸苷激酶转导的供者淋巴细胞(自杀 淋巴细胞)，可被更昔洛韦治疗消融。为 不匹配的亲缘供者移植我们正在评估CD34 精选的骨髓和外周血祖细胞，提供 祖细胞剂量大，免疫反应性T细胞耗尽。 对于无血缘关系的捐赠者或不匹配的移植，我们将研究一种 创新的T细胞耗竭方法，使用系统保留移植物 促进细胞增强植入，同时仍防止 GVHD。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 这一方法的有效性，并试图定义其机制。 我们还将研究下调bcl2基因的维甲酸 并促进细胞凋亡，将提高治疗效果。 最后，我们将检查是否存在最小残留AML 移植治疗后的患者。此项目将与 与本提案中的其他临床项目广泛合作。

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.