Allografting for Lukemia

项目1将用于将在其他项目中开发的概念转换到诊所，并在我们之前的基础上进行 致力于开发新的策略以改善异基因造血患者的预后 细胞移植(HCT)。开发的概念可能会使患有严重血液病的患者受益 但也可以为患有严重自身免疫疾病的患者提供新的治疗策略 疾病和正在接受实体器官移植的人。因此，制定的概念是宽泛的。 并对多个领域产生重大影响。我们将在我们成功翻译的 在项目4中开展的研究中，新的非清髓性全淋巴照射(TLI)方案 抗胸腺细胞球蛋白(ATG)已被探索在急性移植物抗宿主病中显著减少。 (GVHD)与保留移植物抗肿瘤(GVT)反应的风险，TLI/ATG方案将进行比较 对多机构III期首次完全缓解的老年(50-75岁)AML患者进行标准化疗 接受异基因红细胞移植和未接受治疗的人类白细胞抗原相合同胞供者的试验 采用标准化疗(具体目标1)。我们将尝试将TLI/ATG方案增加为两个 预防性应用细胞因子诱导的杀伤(CIK)细胞的重要途径 项目3，努力降低高危髓系恶性肿瘤患者的复发风险(具体目标2)。 第二种方法是将抗CD20的单抗利妥昔单抗与 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 综合治疗将减少慢性移植物抗宿主病和疾病复发(具体目标3)。最后我们会 在调节性T细胞生物学中我们观察到环孢菌素A具有 对Treg功能有重大影响，而雷帕霉素和MMF则不影响。我们将测试以下各项的组合 高危恶性肿瘤患者清髓后进行RAPA/MMF治疗以减少移植物抗宿主病 风险。该项目与所有其他项目交互，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.