Allografting for Lukemia

项目1将用于将其他项目中开发的概念转化为临床，并建立在我们之前的基础上。 致力于开发新的策略，以改善接受同种异体造血干细胞移植的患者的结局。 细胞移植（HCT）。开发的概念可能会使严重血液病患者受益。 但也可以为严重自身免疫性疾病患者提供新的治疗策略。 疾病和进行实体器官移植的患者。因此，所提出的概念是广泛的 并且对许多领域具有重要意义。我们将在成功翻译的基础上， 在项目4中开发的研究中，采用了新型非清髓性全淋巴照射（TLI）方案， 和抗胸腺细胞球蛋白（ATG）已被探索与急性移植物抗宿主病的显着减少 保留移植物抗肿瘤（GVT）反应的GVHD风险，将测试TLI/ATG方案， 在一项多机构III期研究中，在首次达到CR的老年（50-75岁）AML患者中接受标准化疗 在接受同种异体HCT的HLA匹配同胞供体患者和未接受治疗的患者中进行的试验 标准化疗（具体目标#1）。我们将尝试增加TLI/ATG方案，分为两组， 通过利用预防性施用细胞因子诱导的杀伤（CIK）细胞的重要途径， 项目3旨在降低高风险骨髓恶性肿瘤患者的复发风险（具体目标#2）。 第二种方法将是利用抗CD 20单克隆抗体利妥昔单抗与抗CD 20单抗联合。 TLI/ATG在套细胞淋巴瘤和慢性淋巴细胞白血病患者中的应用，以探讨 联合方法将减少慢性GVHD和疾病复发（具体目标#3）。最后我们将 翻译调节性T细胞生物学中的基本观察结果，我们观察到环孢菌素A具有 主要影响Treg功能，而雷帕霉素和MMF没有。我们将测试 高危恶性肿瘤患者清髓性HCT后RAPA/MMF以减少GVHD 风险该项目与所有其他项目相互作用，并利用所有四个核心。

Project 1 will serve to translate concepts developed in other Projects to the clinic and build upon our prior work on developing novel strategies to improve outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). The concepts developed will likely benefit patients with serious hematological malignancies but could also provide novel treatment strategies for patients with severe autoimmune disorders and those undergoing solid organ transplantation. Therefore, the concepts developed are broad and have significant implications for a number of fields. We will build upon our successful translation of the studies developed in Project 4 where the novel non-myeloablative regimen of total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) has been explored with marked reduction in acute graft vs host disease (GVHD) risk with retained graft vs tumor (GVT) responses, The TLI/ATG regimen will be tested as compared to standard chemotherapy in older (ages 50-75) patients with AML in first CR in a multi-institutional phase III trial with those patients with HLA matched sibling donors receiving allogeneic HCT and those without treated with standard chemotherapy (Specific Aim #1). We will attempt to augment the TLI/ATG regimen in two important ways by utilizing prophylactic administration of cytokine induced killer (CIK) cells developed in Project 3 in an effort to reduce relapse risk in patients with high risk myeloid malignancies (Specific Aim #2). A second approach will be to utilize the anti-CD20 monoclonal antibody rituximab in combination with TLI/ATG in patients with mantle cell lymphoma and chronic lymphocytic leukemia to explore whether this combined approach will reduce chronic GVHD and disease relapse (Specific Aim #3). Finally we will translate basic observations in regulatory T cell biology where we have observed that cyclosporine A has a major impact on Treg function whereas rapamycin and MMF do not. We will test the combination of RAPA/MMF following myeloablative HCT in patients with high risk malignancies in an effort to reduce GVHD risk. This Project interacts with all of the other Projects and utilizes all four of the Cores.