ALLOGENEIC LEUKOCYTE INFUSIONS FOR BREAST CANCER

描述：（申请人摘要）在本项目中，申请人将研究 异基因白细胞移植治疗乳腺癌的可行性 自体移植后复发的患者。有 大量数据支持在选择的移植物抗肿瘤效应， 血液恶性肿瘤（CML、AML、多发性骨髓瘤）。然而，明确 在乳腺癌中这种作用的证据尚未得到证实。一些 的机构正在研究异基因干细胞移植， 转移性乳腺癌，以确定是否存在这种影响， 它可以被利用。他正在研究同种异体外周血 从HLA相同或1抗原不匹配的同胞获得的白细胞可 乳腺癌患者在没有准备治疗的情况下进行移植， 自体移植后复发（方案97-017）。UPN 677是一个 一例62岁女性转移性乳腺癌患者接受了自体干细胞移植 1997年4月，高剂量化疗后， 紫杉醇、环磷酰胺、顺铂和BCNU。1998年2月，她 骨进展，一个月后发生肝转移。6月5日， 1998年，她接受了G-CSF动员的外周血输注， 通过荧光原位杂交（FISH），前2周为1-2% 之后开始上升，8月13日达到51%。她死在 1998年8月20日，无抗肿瘤作用的证据。然而，多血统 通过鉴定粒细胞、单核细胞和 供体来源的淋巴细胞。此外，髓系（CFU-GM）和红系 （BFU-E）祖细胞在甲基纤维素中生长，并评估所有集落 通过FISH检测为供体来源。从死后的肝脏中获得的肿瘤是 通过FISH发现含有4%的供体细胞。这些细胞被鉴定为 CD3+、CD19-。申请人建议进一步评估这种治疗方法， 在其他复发性乳腺癌患者中使用这种模式。以下 建议进行相关研究：（1）通过FISH或 循环白细胞、骨髓和祖细胞中的短串联重复序列测定 细胞，（2）输注前和输注后免疫活性的评价， 免疫表型外周血白细胞和特异性免疫功能 研究，（3）通过检查 浸润供体细胞

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.