ALLOGENEIC LEUKOCYTE INFUSIONS FOR BREAST CANCER

描述：(申请者摘要)在这个项目中，申请者将学习 应用同种异体白细胞治疗乳腺癌的可行性研究 自体移植后复发的患者。确实有 相当多的数据支持移植物抗肿瘤效应 恶性血液病(CML、AML、多发性骨髓瘤)。然而，最终的 目前还没有证据表明乳腺癌具有这种效应。一个数字 的机构正在研究异基因干细胞移植 以确定这种影响是否存在以及这种影响是否存在 它可以被利用。他正在研究同种异体外周血 从人类白细胞抗原相合或1抗原不相合的同胞中获得的白细胞可以 乳腺癌患者无准备治疗的植入术 自体移植后复发(协议97-017)。UPN 677是一种 62岁女性转移性乳腺癌患者接受自体干细胞移植 细胞移植于1997年4月在大剂量化疗后使用 紫杉醇、环磷酰胺、顺铂和BCNU。1998年2月，她 在骨骼中进展，一个月后出现肝转移。6月5日， 1998年，她接受了G-CSF动员的外周血液输注，记录在案 通过荧光原位杂交(FISH)，在前两周为1-2% 输液后开始上升，8月13日达到51%。 1998年8月20日，没有抗肿瘤作用的证据。然而，多血统 通过鉴定粒细胞、单核细胞和 供者来源的淋巴细胞。此外，髓系(CFU-GM)和红系 (BFU-E)祖细胞在甲基纤维素中生长，并对所有菌落进行评估 是来自鱼类的捐赠者。从尸检的肝脏中获得的肿瘤是 经FISH检测发现含有4%的供体细胞。这些细胞已被鉴定为 CD3+、CD19-。申请人建议进一步评估这种治疗方法 其他复发乳腺癌患者的治疗方式。以下是 提出了相关研究：(1)FISH或FISH对供体嵌合体的评价 循环白细胞、骨髓和祖细胞的短串联重复序列分析 细胞，(2)输注前后免疫活性的评价 外周血白细胞免疫表型与特异性免疫功能 研究，(3)通过检查评估移植物抗肿瘤活性 正在渗入的供体细胞。

DESCRIPTION: (Applicant's Abstract) In this project, the applicant will study the feasibility of administering allogeneic leukocytes to breast cancer patients who have relapsed after autologous transplantation. There are considerable data supporting a graft-versus-tumor effect in selected hematologic malignancies (CML, AML, multiple myeloma). However, definitive evidence of such an effect in breast cancer has not been demonstrated. A number of institutions are studying allogeneic stem cell transplantation for metastatic breast cancer to determine whether such an effect exists and whether it can be exploited. He is studying whether allogeneic peripheral blood leukocytes obtained from HLA-identical or 1-antigen mismatched siblings can engraft without preparative therapy in patients with breast cancer who have relapsed after autologous transplantation (Protocol 97-017). UPN 677 was a 62-year-old female with metastatic breast cancer who underwent autologous stem cell transplantation in April 1997 after high-dose chemotherapy using paclitaxel, cyclophosphamide, cisplatin and BCNU. In February 1998 she progressed in bone and one month later developed hepatic metastases. On June 5, 1998 she received an infusion of G-CSF-mobilized peripheral blood, documented by fluorescence in-situ hybridization (FISH), was 1-2% for the first 2 weeks after infusion and then began to rise, reaching 51% on August 13. She died on August 20, 1998 without evidence for an antitumor effect. However, multilineage engraftment was documented by identification of granulocytes, monocytes and lymphocytes of donor origin. In addition, myeloid (CFU-GM) and erythroid (BFU-E) progenitors were grown in methylcellulose and all colonies evaluated were of donor origin by FISH. Tumor obtained from the liver post-mortem was found to contain 4% donor cells by FISH. These cells have been identified as CD3+, CD19-. The applicant proposes to further evaluate this therapeutic modality in additional relapsed breast cancer patients. The following correlative studies are proposed: (1) evaluation of donor chimerism by FISH or short tandem repeat assays in circulating leukocytes, marrow and progenitor cells, (2) evaluation of immunocompetence pre- and post-infusion by both immunophenotyping peripheral blood leukocytes and by specific immune function studies, (3) evaluation of graft-versus-tumor activity by examination for infiltrating donor cells.