AIDS RELATED LYMPHOMAS--CLINICAL AND BIOLOGIC STUDIES

该提案的目的是制定更好的治疗方案， HIV相关淋巴瘤患者，并研究 这些疾病。 这将提供一个机会， 临床相关问题，并利用所获得的信息 从生物学研究到设计合理的治疗方案。 这些 目标将通过开展临床试验和相关的 在八个机构组成的联合体内进行实验室研究， 在这方面有临床或基础科学专业知识的机构。 的 该提案的目的是：1）确定生物活性剂量 生长因子白细胞介素3（IL-3）在一项I期试验中， 目的：探讨抗HIV抗体对HIV阳性患者血中p24抗原表达的影响 表情2)确定IL-3、齐多夫定和CHOP的最佳剂量 艾滋病相关淋巴瘤患者的化疗，并进行 对接受治疗的患者进行生活质量研究。3)探讨蛋白酶体抑制剂 新细胞毒素IL-2/白喉毒素（Seragen DAB 486 IL-2） 难治性或复发性HIV相关淋巴瘤患者，并携带 生活质量研究。4)研究艾滋病病毒相关的生物学 a）测定DNA含量、S期和p105核抗原 B）通过分离HIV相关的人的常见的限制性独特型， 淋巴瘤和利用这些用于治疗; c）通过表征组织 d）通过研究选择的原癌基因或EBV序列的样品; HIV“达特”蛋白对人肝癌细胞转化和致瘤性的影响 来源于组织样品的细胞系，和; e）通过研究诱变性， 齐多夫定的作用。5)最后，我们将建立一个中央系统， 病理学审查和数据库收集，以便进行病例 与非HIV淋巴瘤进行比较的对照分析。 这样我们 我认为，改善治疗结果的最终目标是 这些疾病的患者将得到治疗。

The purpose of this proposal is to develop better treatment programs for patients with HIV-related lymphomas and to investigate the biology of these diseases. This will provide an opportunity to link basic biology questions to clinical correlates, and to utilize the information obtained from biologic studies to design rational therapeutic alternatives. These goals will be met by conducting clinical trials and correlative laboratory studies within a consortium of eight institutions, each of which has either clinical or basic science expertise in this area. The aims of the proposal will be 1) To determine the biologically active dose of the growth factor interleukin 3 (IL-3) in a Phase I trial in neutropenic HIV positive patients, and to asses its effect on p24 antigen expression. 2) To determine the optimal dose of IL-3, zidovudine and CHOP chemotherapy in patients with HIV-related lymphoma, and to carry out quality of life studies in patients so treated. 3) To study the effect of the novel cytotoxin IL-2/ diphtheria toxin (Seragen DAB486 IL-2) in patients with refractory or recurrent HIV-related lymphoma, and to carry out quality of life studies. 4) To study the biology of HIV-related lymphoma by a) determining DNA content, S phase and pl05 nuclear antigen expression; b) by isolating restricted idiotypes common to HIV-related lymphomas and utilizing these for therapy; c) by characterizing tissue samples for selected protooncogene or EBV sequences; d) by studying the effect of the HIV "tat" protein on transformation and tumorigenicity of cell lines derived from tissue samples and; e) by studying the mutagenic effect of zidovudine. 5) Finally we will establish a system of central pathology review and data base collection in order to conduct case control analyses for comparison to non HIV lymphomas. In this way we believe that the ultimate goal of improving therapeutic outcome for patients with these diseases will be met.