Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation for metastatic breast cancer: immunologic consequences affecting clinical outcome.
Autologous peripheral blood stem cell transplantation following myeloablative chemotherapy is being increasingly utilized in the treatment of a variety of malignancies. We administered busulfan 16 mg/kg orally, thiotepa 500-700 mg/m2 i.v., and carboplatin 800-1000 mg/m2 i.v. to 56 women with metastatic carcinoma of the breast. Autologous peripheral blood stem cells, which had been collected after a combination of chemotherapy and granulocyte colony-stimulating factor, were infused on day 0. The major toxicities of the conditioning regimen included severe pancytopenia, stomatitis, nausea, emesis, diarrhea, fever, and infection. Transplant-related mortality was 1.8%. The incidence of opportunistic viral infections was 42.9%. Fourteen individuals achieved a complete response. The actuarial survival at 1223 days was 13.7% for the entire group of patients; the actuarial survival at 1009 days was 39.3% among complete responders. The functional status of the immune system was determined following transplantation in a subset of patients. Peripheral blood mononuclear cells were obtained before and after stem cell infusion, and were analyzed phenotypically and functionally. Proliferative and interleukin-2 synthetic ability of these cells was assessed following stimulation with phytohemagglutinin and anti-CD3 antibody. The response to influenza peptides was also ascertained. Proliferative and interleukin-2 synthetic capacity was markedly impaired for over a year. Memory response was virtually absent for up to 2 years following transplantation. The prolonged and marked immunosuppression following this myeloablative regimen was associated with a high incidence of opportunistic viral infections, and may have contributed to disease relapse and progression especially in patients who failed to achieve a complete response following transplantation.
Chakraborty
N
N
Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Bilgrami
S
S
Maness
L
L
Guo
C
C
Perez-Diez
A
A
Mukherji
B
B
Tutschka
P
P
D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D019653:Myeloablative Agonists; D013852:Thiotepa; D016190:Carboplatin; D002066:Busulfan