title: Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98.
abstract: OBJECTIVE
  To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).
  
  
  METHODS
  Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy.
  
  
  RESULTS
  Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%).
  
  
  CONCLUSIONS
  Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
authors.affiliation: Department of Hematology/Oncology, University Children's Hospital, Muenster, Germany. ursula@creutzig.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Johann
authors.initials: J
authors.lastname: Hermann
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Jörg
authors.initials: J
authors.lastname: Ritter
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D007239:Infections / Q000209:etiology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D008942:Mitoxantrone; D015255:Idarubicin; D003630:Daunorubicin