High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy.
High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
Shea
T C
TC
Division of Medical Oncology, University of North Carolina at Chapel Hill.
Mason
J R
JR
Storniolo
A M
AM
Bissent
E
E
Breslin
M
M
Mullen
M
M
Taetle
R
R
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin