LYMPHOKINES AND IMMUNOTHERAPY FOLLOWING AUTOLOGOUS MARROW TRANSPLANTATION

自体骨髓移植后的淋巴细胞因子和免疫治疗

• 批准号: 3751038
• 负责人: ALEXANDER FEFER
• 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/3751038
• 关键词: autologous transplantation; bone marrow transplantation; cell mediated lymphocytolysis test; clinical trials; flow cytometry; human subject; human therapy evaluation; immunomodulators; interleukin 2; leukemia; lymphokine activated killer cell; lymphokines; lymphoma; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer relapse /recurrence

The success of autologous marrow transplantation (AMT) for the treatment of patients with hematologic malignancy is limited largely by a high incidence of disease recurrence after AMT. IL-2 with or without adoptive immunotherapy in the form of ex vivo-generated lymphokine-activated killer (LAK) cells, has induced regression of advanced cancer in some patients, including, primarily, some with hematologic malignancies. This approach could potentially represent a treatment modality which would be non-cross- resistant with chemoradiotherapy conditioning regimens for AMT. IL-2+LAK cells has been used mostly in the presence of large tumor burdens. Our goal is to test the hypothesis that this approach, if used early after AMT in a setting of minimal residual disease, may reduce the posttransplant relapse rate. We have demonstrated that IL-2-responsive LAK precursor cells appear in the circulation early after AMT. We have identified an IL- 2 regimen which is tolerable when administered early after AMT and induces immunomodulatory effects. We have begun to test the feasibility of administering IL-2 plus LAK cells early after AMT. The goals of the studies proposed are to establish a treatment regimen of IL-2 and autologous LAK cells which can be applied to the majority of patients early after AMT for acute leukemia and malignant lymphoma and then to determine the effect of such a regimen on posttransplant relapse rates. Accordingly, the specific aims of this proposal are as follows: 1) to establish the feasibility of administering a regimen of IL-2 and autologous LAK cells early to the majority of patients undergoing AMT for hematologic malignancies, and to compare the relapse rates in patients so treated with appropriate historical controls, and 2) based on the above trial, to conduct a randomized controlled trial of IL-2 and LAK cells versus no consolidative therapy after AMT in patients at high risk for relapse for hematologic malignancies to determine the effect, if any, on the relapse rate.

自体骨髓移植（AMT）的成功治疗 血液系统恶性肿瘤的患者在很大程度上受到高发病率的限制 AMT后疾病复发。 IL-2没有收养 以离体产生的淋巴细胞激活杀手的形式的免疫疗法 （LAK）细胞在某些患者中诱导晚期癌症的消退， 包括一些患有血液学恶性肿瘤的人。 这种方法 可能代表一种治疗方式，这将是非交叉的 AMT的化学放放疗法调节方案具有抗性。 IL-2+LAK 细胞主要用于大肿瘤负担。 我们的 目标是检验以下假设：如果在AMT之后提早使用该方法 在最小残留疾病的情况下，可能会减少移植后 复发率。 我们已经证明了IL-2响应的LAK前体 细胞在AMT之后早期出现在循环中。 我们已经确定了一个IL- 2个方案，在AMT后提早给药并诱导时可容忍的治疗方法 免疫调节作用。 我们已经开始测试 AMT后尽早施用IL-2和LAK细胞。 目标的目标 提出的研究是建立IL-2和 可以早期应用于大多数患者的自体LAK细胞 AMT患有急性白血病和恶性淋巴瘤后，然后确定 这种方案对移植后复发率的影响。 因此， 该提案的具体目的如下：1）建立 管理IL-2和自体LAK细胞方案的可行性 早期大多数接受AMT的血液学患者 恶性肿瘤，并比较与此治疗的患者的复发率 适当的历史控制和2）基于上述试验， 进行IL-2和LAK细胞的随机对照试验与NO AMT后的巩固治疗患者患有高复发风险的患者 血液学恶性肿瘤确定对复发的影响（如果有） 速度。