It is becoming clear that conventional chemotherapy or high-dose chemotherapy with autologous stem cell rescue for metastatic breast cancer provides durable benefit for a relatively small number (less than 10 percent) of women with this disease. Since relapse is thought to represent progression of chemo-resistant disease, the focus of therapy for metastatic breast cancer has turned to immune modulation of cytotoxic therapy. Clinical and experimental evidence from studies of hematologic malignancies and more recently from a transplant model of mouse mammary carcinoma support the existence of an immune-mediated anti-tumor effect following high-dose chemotherapy and allogeneic bone marrow transplantation (BMT). Reduction of transplant-related mortality and reduction of acute and chronic graft-versus-host disease (GVHD) by current techniques of marrow graft engineering at this Center provides the opportunity to offer allogenic BMT to patients with metastatic breast cancer who are poor candidates for existing therapy and who would otherwise receive palliative care only. In addition to being free of contaminating neoplastic cells, marrow allografts may provide additional therapeutic benefit in the form of an immune response to chemo- resistant, residual disease following high dose chemotherapy which is not afforded by the current therapeutic option of autologous stem cell transplants. This project is a Phase II clinical trial of allogeneic BMT for patients who have a poor prognosis for long term remission after autologous BMT. Patients also will be evaluated for evidence of alloimmune reactivity in vitro in a variety of laboratory assays. Results of in vitro assays will be correlated with clinical GVHD and with clinical outcome as measured by progression-free survival to evaluate their possible significance as surrogate markers of graft anti- tumor effect.
