Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy

Purpose: To evaluate whether recombinant human graulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. Patients and Methods: Thirty-seven newly diagnosed patients age 1 to 25 years were randomised to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 mu g/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was greater than or equal to 500/mu L on 2 consecutive days. Results: GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P <.0001), but did not significantly affect the grade of granulocyte nadir. No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival. GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/mu L [range, 3,000 to 288,000] v 59,000/mu L [range, 3,000 to 309,000], P <.0001; median time to recovery > 75,000/mu L, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P <.0001). Conclusion: GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity.