title: Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).
  
  
  RESULTS
  CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.
  
  
  CONCLUSIONS
  G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
authors.affiliation: University Hospital Centers at Marseille, Paris-Trousseau, Paris-St Louis, Rennes, Nancy, Tours, Clermont-Ferrand, Bordeaux, Brest, Bayonne, Amiens, and Rouen, France. gmichel@ap-hm.fr
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: J
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: M F
authors.initials: MF
authors.lastname: Auclerc
authors.forename: C
authors.initials: C
authors.lastname: Mathey
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: E
authors.initials: E
authors.lastname: Legall
authors.forename: P
authors.initials: P
authors.lastname: Bordigoni
authors.forename: J P
authors.initials: JP
authors.lastname: Lamagnere
authors.forename: F
authors.initials: F
authors.lastname: Demeocq
authors.forename: Y
authors.initials: Y
authors.lastname: Perel
authors.forename: A
authors.initials: A
authors.lastname: Auvrignon
authors.forename: C
authors.initials: C
authors.lastname: Berthou
authors.forename: F
authors.initials: F
authors.lastname: Bauduer
authors.forename: B
authors.initials: B
authors.lastname: Pautard
authors.forename: P
authors.initials: P
authors.lastname: Schneider
authors.forename: G
authors.initials: G
authors.lastname: Schaison
authors.forename: G
authors.initials: G
authors.lastname: Leverger
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009503:Neutropenia / Q000139:chemically induced* / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D011994:Recombinant Proteins; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000517:prevention & control; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate