ALLOGENEIC BONE MARROW TRANSPLANTATION FOR CML

这个项目包括五个目标，旨在测试假设的改进 异基因血液和骨髓移植的结果。该项目 致力于创新以提高制剂的治疗指数 方案，优化同种异体移植物的成分，增强 预防严重移植物抗白血病的研究进展 寄主疾病。在目标1中，我们测试了持久缓解可以 通过诱导移植物抗白血病作为主要治疗方法来实现 以及这一策略是否能提高无病存活率。目标2我们 扩展我们的白消安静脉制剂的开发和试验 静脉注射白消安和环磷酰胺的制备方案是否 药代动力学指导剂量可提高白血病患者的无瘤存活率 有匹配兄弟姐妹捐赠者的慢性期患者。在目标3中，我们扩展了 我们先前的研究表明CD8耗尽可以有效地诱导GVL 供者淋巴细胞输注及最佳生物剂量的确定 进一步研究的目标是通过移植诱导完全缓解- 抗宿主疾病。我们将继续比较它们的疗效与 用于诱导GVL的普通淋巴细胞。在目标4中，我们翻译 项目4和项目6正在开发创新方法，使之成为人类 临床试验，测试胸苷激酶转导的供者 供者淋巴细胞输注后淋巴细胞输注可消除移植物抗宿主病 并评价巨糖T细胞去除的血液干细胞的疗效 人类白细胞抗原半相合供者的移植。在Aim 5中，我们 将评估地西他滨作为骨髓抑制药的疗效 晚期慢性粒细胞白血病患者和配对同胞的准备方案 捐赠者。

This project includes five aims directed to testing hypotheses improving the outcome of allogeneic blood and marrow transplantation. The project addresses innovations to improve the therapeutic index of the preparative regimen, optimize the composition of the allograft and enhance the development of graft versus leukemia while preventing severe graft versus host disease. In Aim 1, we test the hypothesis that durable remissions can be achieved by induction of graft-versus-leukemia as primary treatment for CML and whether this strategy can improve disease free survival. Aim 2 we extend our development of an intravenous formulation of busulfan and test whether a preparative regimen of IV busulfan and cyclophosphamide with dose guiding by pharmacokinetics can improve leukemia free survival for chronic phase patients with matched sibling donors. In Aim 3, we extend our prior studies demonstrating effective GVL induction with CD8 depleted donor lymphocyte infusions and determine the optimal biologic dose for further study with a goal of inducing complete remission with graft- versus-host disease. We will go on to compare their efficacy versus unfractionated lymphocytes for induction of GVL. In Aim 4, we translate innovative approaches being developed in projects 4 and 6 into human clinical trials, testing whether thymidine kinase transduced donor lymphocyte infusions can abrogate GVHD after donor lymphocyte infusions and to evaluate the efficacy of megadose T-cell depleted blood stem cell transplantation for patients with HLA-haploidentical donors. In Aim 5, we will evaluate the efficacy of decitabine as a myelosuppressive agent in preparative regimens for patients with advanced CML and a matched sibling donor.