Effects of recombinant human granulocyte-macrophage colony-stimulating factor in an intensive treatment program for children with Ewing's sarcoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Luksch
R
R
Pediatric Oncology Unit, Istituto Nazionale Tumori, via G. Venezian 1, 20133 Milan, Italy. luksch@istitutotumori.mi.it
Massimino
M
M
Cefalo
G
G
Lombardi
F
F
Ferrari
A
A
Casanova
M
M
Gandola
L
L
Terenziani
M
M
Spreafico
F
F
Fossati-Bellani
F
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007223:Infant; D008297:Male; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor