Prolonged disease control by nonmyeloablative allogeneic transplantation for metastatic breast cancer

• Published in: Bone marrow transplantation (Basingstoke) Vol. 44; no. 2; pp. 81 - 87
• Main Authors: de Souza, J A, Davis, M L, Rondon, G, Cheng, Y C, Jones, R B, Champlin, R E, Ueno, N T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2009; Nature Publishing Group
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone diseases; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Breast cancer; Breast carcinoma; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Care and treatment; Cell Biology; Chemotherapy; Conditioning; Development and progression; Disease control; Dose-Response Relationship, Drug; Drug Administration Schedule; Engraftment; Female; Fludarabine; Follow-Up Studies; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Gynecology. Andrology. Obstetrics; Hematology; Hematopoietic stem cells; Humans; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Internal Medicine; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Melphalan; Metastases; Metastasis; Middle Aged; Mortality; Neoplasm Metastasis - therapy; original-article; Patients; Peripheral Blood Stem Cell Transplantation - adverse effects; Prospective Studies; Public Health; Stem cell transplantation; Stem Cells; Survival; Survival Rate; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Tumors; United States; graft-versus-tumor effect; nonmyeloablative regimen; metastatic breast cancer; allogeneic hematopoietic cell transplantation; Breast disease; Hematology; Graft versus tumor reaction; Stem cell; Hematopoietic cell; Homograft; Breast cancer; Non myeloablative treatment; Metastasis; Malignant tumor; Mammary gland diseases; Graft; Advanced stage; Therapeutic protocol; Cancer; Prolonged
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2009.101

We found earlier that high-dose chemotherapy with Allo-SCT produced a tumor response in patients with chemorefractory metastatic breast cancer. In this study, we examined the efficacy and toxicity of nonmyeloablative allogeneic PBSC transplantation in patients with chemosensitive metastatic breast cancer. Twelve patients with metastatic breast carcinoma who had stable disease after standard-dose chemotherapy and six who had a partial response underwent allogeneic transplantation. The conditioning regimen consisted of reduced-intensity fludarabine and melphalan. All patients achieved engraftment and hematopoietic recovery. Nine patients developed grade II or higher acute GVHD; seven of these nine responded to immunosuppressive therapy. Fourteen patients developed chronic GVHD. The treatment-related mortality rate was 11%. With a median follow-up of 565 days, the median survival duration was 643 days and the median progression-free survival duration was 202 days. Two patients are alive with a complete response 1555 and 2526 days after SCT, and one patient is alive with progressive bone disease at day 1118. We conclude that among patients with chemotherapy-sensitive metastatic breast cancer, a fraction will achieve a durable complete response after SCT with a reduced-intensity conditioning regimen. The question remains how to improve the overall efficacy and reduce the mortality rate for this approach.