Autografting for Lymphoma

自体移植治疗淋巴瘤

• 批准号: 8260362
• 负责人: SANDRA J. HORNING
• 金额: $ 35.17万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260362
• 关键词: Acute Graft Versus Host Disease; Allogenic; Antithymoglobulin; Autologous; Autologous Transplantation; B-Cell Lymphomas; B-Lymphocytes; Biology; Bone Marrow Transplantation; Cell Transplantation; Cells; Clinic; Clinical Investigator; Dendritic Cells; Development; Diffuse; Disease; Disease remission; Disease-Free Survival; Exclusion; Functional Imaging; Genetic; Goals; Graft-Versus-Tumor Induction; Hematopoietic; Immune; Immune Targeting; Immune response; Immunoglobulin Idiotypes; Immunotherapy; Incidence; Killer Cells; Laboratories; Lymphatic Irradiation; Lymphoma; Mantle Cell Lymphoma; Measures; Mediating; Molecular; Morbidity - disease rate; Neoadjuvant Therapy; Non-Hodgkin' s Lymphoma; Patients; Physiologic pulse; Positron-Emission Tomography; Pre-Clinical Model; Principal Investigator; Program Research Project Grants; Randomized; Recurrence; Recurrent disease; Refractory; Regimen; Relapse; Residual Tumors; Risk; System; T-Lymphocyte; Toxic effect; Translating; Transplantation; Tumor Burden; Universities; Vaccinated; Vaccination; Vaccines; base; chemotherapy; conditioning; cytokine; disorder control; disorder risk; experience; fluorodeoxyglucose positron emission tomography; high risk; improved; leukemia/lymphoma; mortality; novel; novel therapeutics; older patient; peripheral blood; rituximab; standard care; tositumomab; tumor

Autologous hematopoietic cell transplantation (AHCT) is the standard treatment for the most common type of non-Hodgkin's lymphoma, diffuse large B-cell (DLBCL), that recurs or is primarily refractory to induction therapy, and the application of AHCT following induction therapy for mantle cell lymphoma (MCL) has been shown to prolong diseas'e remission. Despite excellent cytoreduction, relapse occurs continuously in MCL and in about half of DLBCL cases. The idiotype unique to each B-cell lymphoma is a specific target that we have successfully pursued for vaccination. In Aim 1, we plan to vaccinate with idiotype-pulsed dendritic cells after AHCT in MCL, building upon our experience in developing and using these cells after transplantation (IND #11227), together with administration of primed T-cells, in order to optimize the likelihood of an effective, durable immune response. We will measure the effects of vaccination by molecular assessment of tumor burden in the peripheral blood and by determination of the immune response. In Aim 2, we will take advantage of advances in functional imaging with FDG-PET that allow the distinction of DLBCL patients with a very high rate of relapse after standard AHCT. Utilizing existing systems for central PET review at Stanford University, we will define very high risk DLBCL patients on the basis of PET-positive disease after salvage chemotherapy and plan post-AHCT immunotherapy on the basis of genetic randomization. In high risk DLBCL patients with HLA matched donors (Aim 2.1), we will pursue non- myeloablative allogeneic HCT utilizing a novel conditioning regimen consisting of total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) developed in Project 4 and translated in Project 1 of this Program Project Grant. Our experience with this regimen suggests that graft versus tumor effects are retained but the incidence of acute graft versus host disease (GVHD) and treatment-related mortality is reduced. For those PET-positive patients without an available donor (Aim 2.2), we plan to study cytokine-induced killer (CIK) cells as a post-AHCT immunotherapy, building on our previous experience with CIK cells in Project 3, which has been translated in the autologous setting in this Project. The unifying hypothesis in Project 2 is that lymphoma-specific immunotherapy applied after cytoreduction and tumor control is established with conventional AHCT will improve event-free survival in patients with lymphoma at high risk of recurrence. Our goals are to develop such immune-based strategies to reduce the risk of disease relapse after AHCT that could be broadly applied to non-Hodgkin's lymphoma patients. Project 2 interacts with Projects 1, 3, 4, 6, and 8 and is supported by all of the Cores of this Program Project Grant.

自体造血细胞移植（AHCT）是目前最多的标准治疗方法