TY - JOUR
T1 - Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation for metastatic breast cancer
T2 - Immunologic consequences affecting clinical outcome
AU - Chakraborty, N. G.
AU - Bilgrami, S.
AU - Maness, L. J.
AU - Guo, C.
AU - Perez-Diez, A.
AU - Mukherji, B.
AU - Tutschka, P.
N1 - Funding Information:
This work was supported by a grant from the University of Connecticut Health Center Research Council (6-33071) and in part by National Institute of Health (CA 613980). We are indebted to Mrs Joyce Fritz for her expertise in the preparation of this manuscript.
PY - 1999
Y1 - 1999
N2 - 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 stent 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 32.9%. 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.
AB - 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 stent 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 32.9%. 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.
KW - Breast cancer
KW - Immunosuppression
KW - Myeloablative chemotherapy
KW - Stem cell transplant
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U2 - 10.1038/sj.bmt.1701999
DO - 10.1038/sj.bmt.1701999
M3 - Article
C2 - 10516693
AN - SCOPUS:0032725491
SN - 0268-3369
VL - 24
SP - 837
EP - 843
JO - Bone marrow transplantation
JF - Bone marrow transplantation
IS - 8
ER -