IMMUNOTHERAPY AFTER AUTOLOGOUS MARROW TRANSPLANTION

自体骨髓移植后的免疫治疗

• 批准号: 2099253
• 负责人: ALEXANDER FEFER
• 金额: $ 12.9万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2099253
• 关键词: acute lymphocytic leukemia; autologous transplantation; bone marrow transplantation; clinical trials; human subject; human therapy evaluation; interleukin 2; lymphokine activated killer cell; neoplasm /cancer immunotherapy; nonHodgkin's lymphoma

The success of autologous marrow transplantation (AMT) for the treatment of patients with leukemia or lymphoma is limited largely by the high incidence of recurrence of the malignancy after AMT. Immunotherapy in the form of recombinant human IL-2 used alone or with ex vivo-generated lymphokine activated killer (LAK) cells has induced regression of advanced cancer in some patients and remissions in some patients with acute leukemia or malignant lymphoma. IL-2/LAK therapy could potentially represent a treatment modality which would not be cross-resistant with the chemoradiotherapy used as a preparative regimen for AMT. Our goal is to test the hypothesis that this approach, used early after AMT in a setting of minimal residual disease, i.e., as consolidative immunotherapy, may decrease the relapse rates. We have already (a) demonstrated that IL-2-responsive LAK precursor cells are detectable in the circulation early after AMT; (b) identified an IL-2 regimen which is tolerable and induces immunomodulatory effects when administered early after AMT; and (c) completed a feasibility trial of the IL-2 regimen plus ex vivo-generated autologous LAK cells in patients who have undergone AMT for advanced hematologic malignancy -- with encouraging preliminary clinical results. The specific aim of this proposal is to perform a randomized controlled trial of consolidative immunotherapy with IL-2 + LAK cells vs. no IL-2/LAK after AMT in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia so as to determine the effect, if any, on their high relapse rates.

自体骨髓移植（AMT）的成功 白血病或淋巴瘤的患者在很大程度上受到高度限制 AMT后恶性肿瘤复发的发生率。 免疫疗法 重组人IL-2的形式单独使用或与离体生成的形式 淋巴因子活化杀手（LAK）细胞已诱导的消退 某些患者的晚期癌症以及一些患者的减免 急性白血病或恶性淋巴瘤。 IL-2/LAK治疗可能有可能 代表一种治疗方式，不会与 化学放射疗法用作AMT的制备方案。 我们的目标 是为了检验以下假设：这种方法在AMT之后早期使用 设置最小残留疾病，即作为巩固 免疫疗法可能会降低复发率。 我们已经（a） 证明IL-2响应的LAK前体细胞在 AMT早期的循环； （b）确定了IL-2方案 早期给药时可耐受和诱导免疫调节作用 AMT之后； （c）完成了IL-2方案加的可行性试验 经过体内生成的自体Lak细胞的患者 用于先进的血液学恶性肿瘤 - 令人鼓舞的初步 临床结果。 该提议的具体目的是执行 与IL-2 +综合免疫疗法的随机对照试验 非霍奇金淋巴瘤患者AMT后的LAK细胞与NO IL-2/LAK无IL-2/LAK 和急性淋巴细胞白血病，以确定效果（如果有） 关于他们的高复发率。