Interleukin-2 and granulocyte-macrophage-colony-stimulating factor immunomodulation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer.

Abstract

Immunomodulation with cytokines was used to improve the result of high-dose chemotherapy (HDC)/autologous hematopoietic stem cell transplantation (AHST). We examined the use of IL-2 and growth factors for mobilization, ex vivo activation of peripheral blood stem cell (PBSC) and maintenance therapy after HDC/AHST in metastatic breast cancer. Eligible patients with metastatic breast cancer for HDC/AHST were assigned to 1 of 3 protocols for PBSC mobilization: G-CSF (group 1); IL-2 + G-CSF (group 2); or IL-2 + G-CSF + GM-CSF (group 3). HDC with cyclophosphamide, carmustine and thiotepa was given from day -7 to -5. PBSCs were treated ex vivo with IL-2 for 24 h and reinfused on day 0. Maintenance therapy included low-dose IL-2, followed by 2 courses of intermediate-dose IL-2. GM-CSF was given from day 1 until neutrophil recovery. Thirty-four patients (10 in group 1, 14 in group 2, and 10 in group 3) were included. Comparable numbers of CD34(+) cells were collected from all 3 groups; incremental increases of CD3(+) cells were collected from groups 1 to 2 and to 3 (p = 0.03). Major adverse effects from IL-2 were fever, hypotension and fatigue; no treatment-related mortality was seen. At a median follow-up of 790.5 days (range 150-2,722 days), median progression-free survival was 434 days and median overall survival was 1,432 days. Estimated 3-year progression-free and overall survival rates were 31 and 57%. Our study suggested that the use of IL-2 and growth factors immunomodulation with HDC/AHST was feasible with comparable survival rates.

• Authors: Yee Chung Cheng, Gabriela Rondón, Leah F Sanchez, John D McMannis, Daniel R Couriel, Marcos J de Lima, Chitra Hosing, Issa F Khouri, Sergio A Giralt, Richard E Champlin, Naoto T Ueno
• Journal: International journal of hematology (Int J Hematol) Vol. 90 Issue 5 Pg. 627-634 (Dec 2009) ISSN: 1865-3774 [Electronic] Japan
• PMID: 19998065 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (mortality, pathology, therapy)
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, therapeutic use)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Immunomodulation
• Interleukin-2 (administration & dosage, therapeutic use)
• Middle Aged
• Neoplasm Metastasis
• Survival Rate
• Transplantation, Autologous
• Treatment Outcome
• Young Adult