ALLOGENIC BLOOD AND MARROW TRANSPLANT FOR ACUTE MYELOGENOUS LEUKEMIA

大剂量放化疗联合异基因造血干细胞移植 移植是AML的有效治疗方法。这种方法 被认为是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的方法， 旨在改善同种异体移植的结果。 这包括评价地西他滨作为一种新的药物， 用同种异体外周血祖细胞的制备方案 在配对的兄弟姐妹中进行细胞移植最近取得的令人鼓舞的成果 与供体淋巴细胞输注表明， 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 有利于这将在老年患者中进行研究， 匹配的同胞供体，主要分析终点为 移植、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， 相同的兄弟姐妹;我们研究了两种创新的方法来实现 在这种情况下没有GVHD的移植。GVHD的预防 接受同种异体移植的患者将使用 胸苷激酶转导的供体淋巴细胞（自杀性 淋巴细胞），其可以通过更昔洛韦治疗消除。为 不匹配的相关供体移植，我们正在评估CD 34 选择的骨髓加外周血祖细胞， 大剂量祖细胞和全反应性T细胞耗尽 对于无关供体或不匹配的移植，我们将研究 创新的T细胞去除方法，使用系统保留移植物 促进细胞增强植入，同时仍然防止 GVHD。对于复发的患者，我们报告了独特的观察结果， G-CSF治疗可以恢复缓解;我们进一步研究 这种方法的有效性，并试图定义其机制。 我们还将研究下调bcl-2的视黄酸是否 并增强细胞凋亡，将增强治疗效果。 最后，我们将检查中是否存在最低限度的残留AML 移植治疗后的患者。该项目相互作用 与本提案中的其他临床项目进行了广泛的合作。

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.