RADIOIMMUNOTHERAPY OF LYMPHOMA

描述：（改编自研究者摘要）晚期 低度恶性淋巴瘤不能用常规疗法治愈， 患有这种疾病的人最终死于疾病或治疗并发症。 因此，需要新的治疗方法。 我们已经证明了 用131-I标记的抗B1（抗CD 20）进行放射免疫治疗（RIT）， 在几乎所有患者的主要和持久的肿瘤反应中（13/13，10 完全缓解）与化疗难治性低级别淋巴瘤。 我们 因此，建议测试这种治疗方法将是 作为低级别淋巴瘤的一线治疗特别有效， 在既往未经治疗的患者中进行II期临床试验 晚期低度恶性淋巴瘤 为了进一步确定这种方法的有效性， 治疗，我们将寻求确定是否检测最小 残留病（MRD）的分子生物学技术有助于预测 缓解期。 具体来说，我们将测试PCR的使用 涉及bcl-2的t（14;18）染色体易位的扩增 原癌基因（其代表高达85%的滤泡上皮细胞的克隆标记物） 淋巴瘤），以连续检测骨髓和外周血中的MRD。 的 这些研究的结果不仅将产生关于 这种治疗的细胞减少能力，但也可能有助于确定 患者可能会受益于未来的额外或连续治疗 问题研究 最后，由于这种治疗的剂量限制性毒性是 骨髓抑制，我们希望利用这一独特的机会， 继续研究RIT对以下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可能对不同成分产生不同影响的假设 通过检查对干细胞的短期和长期影响， 细胞，定向祖细胞和支持基质细胞通过骨 在RIT后的不同时间进行骨髓培养试验。 这些研究 应该产生重要的和明确的信息， RIT诱导的骨髓抑制机制-骨髓对RIT的耐受性 重复剂量、更高剂量或其他可能 与131-I-抗B1联合使用或在131-I-抗B1之后使用。 放射剂量测定研究将同时进行，以更清楚地 定义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有助于回答 关于RIT的重要基本问题，并帮助开发这种新的， 治疗淋巴瘤的有前途的策略。

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.