title: Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group.
abstract: OBJECTIVE
  In pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Münster Study Group.
  
  
  METHODS
  Patients with relapsed or primary refractory non-French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years).
  
  
  RESULTS
  The complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good (≤ 20% leukemic blasts) in 80% of patients randomly assigned to FLAG/DNX and 70% for patients randomly assigned to FLAG (P = .04). Concerning secondary end points, the CR rate was 69% with FLAG/DNX and 59% with FLAG (P = .07), but overall survival was similar. However, core-binding factor (CBF) AML treated with FLAG/DNX resulted in pOS of 82% versus 58% with FLAG (P = .04). Grade 3 to 4 toxicity was essentially similar in both groups.
  
  
  CONCLUSIONS
  DNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far.
authors: Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1117, NL-1081HV Amsterdam, the Netherlands. gjl.kaspers@vumc.nl
authors: Gertjan J L
authors: GJ
authors: Kaspers
authors: Martin
authors: M
authors: Zimmermann
authors: Dirk
authors: D
authors: Reinhardt
authors: Brenda E S
authors: BE
authors: Gibson
authors: Rienk Y J
authors: RY
authors: Tamminga
authors: Olga
authors: O
authors: Aleinikova
authors: Hortensia
authors: H
authors: Armendariz
authors: Michael
authors: M
authors: Dworzak
authors: Shau-Yin
authors: SY
authors: Ha
authors: Henrik
authors: H
authors: Hasle
authors: Liisa
authors: L
authors: Hovi
authors: Alexei
authors: A
authors: Maschan
authors: Yves
authors: Y
authors: Bertrand
authors: Guy G
authors: GG
authors: Leverger
authors: Bassem I
authors: BI
authors: Razzouk
authors: Carmelo
authors: C
authors: Rizzari
authors: Petr
authors: P
authors: Smisek
authors: Owen
authors: O
authors: Smith
authors: Batia
authors: B
authors: Stark
authors: Ursula
authors: U
authors: Creutzig
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015986:Confounding Factors, Epidemiologic; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008081:Liposomes; D008297:Male; D016017:Odds Ratio; D012074:Remission Induction; D012107:Research Design; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; D003630:Daunorubicin