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.
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.
Cheng
Yee Chung
YC
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Division of Neoplastic Diseases and Related Disorders, Medical College of Wisconsin, Milwaukee, WI, USA.
Rondón
Gabriela
G
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Sanchez
Leah F
LF
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
McMannis
John D
JD
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Couriel
Daniel R
DR
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
de Lima
Marcos J
MJ
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Hosing
Chitra
C
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Khouri
Issa F
IF
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Giralt
Sergio A
SA
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Champlin
Richard E
RE
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Ueno
Naoto T
NT
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. nueno@mdanderson.org.|Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. nueno@mdanderson.org.
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D056747:Immunomodulation; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor