Comparative effects of three cytokine regimens after high-dose cyclophosphamide: Granulocyte colony-stimulating factor, granulocyte- macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF

Purpose: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m²), given as the first step of a high-dose sequential chemotherapy. Patients and Methods: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 μg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34⁺ cells and granulocyte-macrophage colony- forming units (CFU-GM). Results: Neutrophil recovery was faster in arm I as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P = .028). The peak of CD34⁺ cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P = .0002), whereas the median peak value of CD34⁺ cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. Conclusion: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.