ALLOGENEIC LEUKOCYTE INFUSIONS FOR BREAST CANCER

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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.