Effects of recombinant human granulocyte-macrophage colony-stimulating factor in an intensive treatment program for...

A treatment program including polychemotherapy at progressively escalating doses and sequential hemi-body irradiation (HBI) was adopted between 1987-1994 at our Pediatric Unit for high risk Ewing's sarcoma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to the treatment program in a phase II study fashion to evaluate, in a pediatric setting, its tolerability, as well as its impact on drug dose escalation and on the need for supportive care.

The study was open-label and sequential; GM-CSF administration (5 microg/Kg s.c./d x10) was planned after each chemotherapy cycle and after each HBI session in 18 consecutive patients (group A). Thirty-eight additional patients (group B) were treated by the same therapeutic program, without GM-CSF. In 12 patients (6 in each group) long-term bone marrow cultures (LTBMC) were performed to evaluate the myeloproliferative potential throughout the chemotherapeutic program.

Seven of 18 (39%) patients experienced side effects from GM-CSF; 3/7 discontinued GM-CSF due to anaphylactic symptoms. The degree of neutropenia, as well as the frequency of infectious episodes and the need for supportive care were significantly lower in group A than in group B. Iatrogenic thrombocytopenia, and the possibility of performing drug-dose escalation were similar in the two groups. The 5-year event-free survival probabilities for group A and B were similar. LTBMC showed that the chemotherapy-related depletion of myeloid precursors could be more pronounced in patients receiving GM-CSF cyclically.

In this series, GM-CSF was shown to be effective on iatrogenic neutropenia and related complications, with no impact on thrombopoiesis, drug dose escalation and outcome.