RADIOIMMUNOTHERAPY OF LYMPHOMA

描述：(改编自《调查员摘要》)高级阶段 低度恶性淋巴瘤不能用常规疗法和患者治愈。 患有这种疾病的人最终死于疾病或治疗的并发症。 因此，需要新的治疗方法。我们现在已经演示了 131I标记抗B1(抗CD20)的放射免疫治疗(RIT)结果 几乎所有患者的主要和持久的肿瘤反应(13/13，10 完全缓解)与化疗耐药的低级别淋巴瘤。我们 因此建议检验这样一种假设，即这种治疗 作为低级别淋巴瘤的一线治疗，尤其有效 对以前未接受治疗的患者进行II期临床试验 晚期低度恶性淋巴瘤。为了进一步定义这一功能的有效性 治疗后，我们将寻求确定是否检测到最低限度 分子生物学技术有助于预测残留病(MRD) 减刑期限。具体来说，我们将测试聚合酶链式反应的使用 涉及bcl2的t(14；18)染色体易位的扩增 原癌基因(代表高达85%的卵泡的克隆标记 淋巴瘤)，以连续检测骨髓和外周血中的MRD。这个 这些研究的结果不仅将提供关于 这种治疗的细胞还原能力，也可能有助于确定 患者将来可能会从额外或辅助治疗中受益。 学习。最后，由于这种治疗的剂量限制毒性是 骨髓抑制，我们希望利用这个独特的机会 继续研究RIT对慢性粒细胞白血病患者造血功能的影响 以前没有接触过骨髓改变剂。我们将测试 RIT可能对不同成分有不同影响的假设 通过检查骨髓对干细胞的短期和长期影响 细胞、承诺的祖细胞和支持通过骨的基质细胞 在RIT后不同时间进行骨髓培养。这些研究 应该产生关于基本的和明确的信息 RIT诱导骨髓抑制的机制--骨髓耐受 重复剂量，更高剂量，或其他可能是 与131-I-抗-B1结合使用或在131-I-抗B1之后使用。 放射性核素测量研究将同时进行，以更清楚地 确定有关骨髓毒性的剂量-反应关系以及 肿瘤反应。这些拟议的综合研究应该有助于回答 有关RIT的重要基本问题，并帮助开发这一新的和 总体来说，治疗淋巴瘤的策略前景看好。

DESCRIPTION: (Adapted from the Investigator's Abstract) Advanced-stage low-grade lymphoma is not curable with conventional therapy and patients with this disease ultimately die of disease or complications of treatment. Therefore, new therapeutic approaches are needed. We have now demonstrated that radioimmunotherapy (RIT) with 131-I-labeled anti-B1 (anti-CD20) results in major and durable tumor responses in virtually all patients (13 of 13, 10 complete remissions) with chemotherapy-refractory low-grade lymphoma. We therefore propose to test the hypothesis that this treatment would be especially effective as front-line treatment for low-grade lymphoma by conducting a phase II clinical trial in patients with previously untreated advanced-stage low-grade lymphoma. To further define the efficacy of this treatment, we will seek to determine whether the detection of minimal residual disease (MRD) by molecular biological techniques help predict duration of remission. Specifically, we will test the use of PCR amplification of the t(14;18) chromosomal translocation involving the bcl-2 proto-oncogene (which represents a clonal marker for up to 85% of follicular lymphomas) to serially detect MRD in bone marrow and peripheral blood. The results of these studies will not only yield information on the cytoreductive power of this treatment, but also may help determine which patients may benefit from additional or adjunctive therapy in future studies. Finally, since the dose-limiting toxicity of this treatment is myelosuppression, we wish to take advantage of this unique opportunity to continue our studies on the effects of RIT on hematopoiesis in patients who have not been previously exposed to marrow-altering agents. We will test the hypothesis that RIT may have different effects on different components of the bone marrow by examining the short-term and long-term effects on stem cells, committed progenitor cells, and supporting stromal cells through bone marrow culture assays performed at various times after RIT. These studies should yield important and definitive information on the fundamental mechanisms of RIT-induced myelosuppression the tolerance of bone marrow to repeated doses, higher doses, or to other cytotoxic agents which might be used in combination with or used subsequent to 131-I-anti-B1. Radiodosimetric studies will be conducted concurrently to more clearly define dose-response relationships concerning marrow toxicity as well as tumor response. These proposed integrated studies should help answer important fundamental questions regarding RIT and help develop this new and promising strategy for the treatment of lymphomas in general.