ALTERNATE MARROW DONORS FOR PATIENTS LACKING AN HLA-FAMILY MEMBER

缺乏 HLA 家族成员的患者的替代骨髓捐赠者

• 批准号: 3771400
• 负责人: JOHN A HANSEN
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3771400
• 关键词: CD3 molecule; MHC class II antigen; acute leukemia; acute myelogenous leukemia; bone marrow transplantation; chronic myelogenous leukemia; colony stimulating factor; diagnosis design /evaluation; family genetics; graft versus host disease; histocompatibility typing; homologous transplantation; human morbidity; human mortality; human subject; human therapy evaluation; immunosuppression; interleukin 2; isoantigen; major histocompatibility complex; methotrexate; myelogenous leukemia; neoplasm /cancer immunotherapy; neoplasm /cancer remission /regression; polymerase chain reaction; serotyping; transplant rejection; transplantation resource /registry /referral center

The long-term objective of this project is to develop new methods for marrow transplantation using alternative donors for patients with hematologic malignancies who lack an HLA identical sibling. Specific aims are: 1) to decrease morbidity and non-relapse mortality in transplants from unrelated donors. Human recombinant GM-CSF administered from day 0 to day +27 will be evaluated in a placebo-controlled, randomized, double-blind, phase III trial for the effect on engraftment, infection and regimen related toxicity. 2) to compare the outcome of transplants from unrelated donors who are partially HLA mismatched to those who are phenotypically HLA matched. Donors who differ by one HLA class I locus if the mismatched antigens fall within a crossreactive group, or differ by an HLA-DRB1 locus if the mismatched alleles fall within a single serologically defined specificity will be used for patients below 36 years of age. The rates of acute GVHD, transplant-related mortality and survival will be compared for patients with same age, disease, diagnosis and stage, and GVHD prophylaxis but different degree of HLA matching and 3) to decrease graft rejection and GVHD in recipients of HLA haplomismatched family member grafts. T-cell receptor/CD3 complex-specific antibody BC3 administered for 14 days beginning just before the marrow infusion will be evaluated in a phase I/II study to facilitate engraftment in patients with a positive anti-donor lymphocyte crossmatch, a group with the highest risk of graft rejection. 4) develop and assess functional assays that measure donor immune responses to the recipient's alloantigens, and determine if these assays will be useful for predicting GVHD and facilitating donor selection.

该项目的长期目标是开发新方法 使用替代供体为患有以下疾病的患者进行骨髓移植 缺乏 HLA 相同同胞的血液恶性肿瘤。 具体目标 是： 1) 降低移植物的发病率和非复发死亡率 无关的捐助者。 从第 0 天到第 1 天施用人重组 GM-CSF +27 将在安慰剂对照、随机、双盲、 对植入、感染和治疗方案影响的 III 期试验 相关毒性。 2) 比较非亲属捐献者的移植结果 部分 HLA 不匹配的人与表型 HLA 匹配的人。 如果不匹配的抗原下降，则捐赠者因一个 HLA I 类基因座而不同 在交叉反应组内，或者 HLA-DRB1 位点不同，如果 不匹配的等位基因属于单一血清学定义的特异性 将用于36岁以下的患者。 急性 GVHD 发生率， 将比较患者的移植相关死亡率和生存率 具有相同的年龄、疾病、诊断和分期以及 GVHD 预防，但 不同程度的HLA匹配 3) 减少HLA受者的移植物排斥和GVHD 单倍体不匹配的家庭成员移植物。 T 细胞受体/CD3 复合物特异性 在骨髓之前开始注射抗体 BC3，持续 14 天 输注将在 I/II 期研究中进行评估，以促进植入 在抗供体淋巴细胞交叉配型呈阳性的患者中，一组 移植物排斥的风险最高。 4) 开发和评估测量供体免疫反应的功能测定 到接受者的同种异体抗原，并确定这些测定是否将被 对于预测 GVHD 和促进捐赠者选择很有用。