title: Re-induction with L-DNR/FLAG improves response after AML relapse, but not long-term survival.
abstract: BACKGROUND
  According to the results of the international study Relapsed AML 2001/01 response was better after re-induction with L-DNR/FLAG (liposomal daunorubicin, fludarabine, cytarabine, G-CSF) compared to FLAG only but survival rate was not improved. However, the findings might be group-specific.
  
  
  METHODS
  Patient characteristics, actual therapy given and long-term course of the disease in 155 pediatric patients (including non-randomized) with first relapse and 10 primary nonresponders treated in Germany were analyzed.
  
  
  RESULTS
  Overall 4-year survival rates after relapse were similar in the 2 treatment groups L-DNR/FLAG and FLAG (0.43 ± 0.05 vs. 0.47 ± 0.06, p(log-rank)=0.47). The rate of randomization was low (65%) and 5% of the 101 randomized patients changed the treatment arm. Therefore, induction was based in 40% patients on an individual decision with preference for L-DNR/FLAG. There were less patients with favorable cytogenetics and morphology in the L-DNR/FLAG-group (p<0.04). Response to the first re-induction course at day 28 tended to be more unfavorable with FLAG only. In this patient group protocol intensifications were more frequent as compared to the L-DNR/FLAG-group (p=0.07), and late CR could be achieved after intensification in 9/18 poor responding patients.
  
  
  CONCLUSIONS
  The initial selection bias of relapse patients with unfavorable risk factors to the disadvantage of the L-DNR/FLAG-group and the more drug- and time-intensive treatment after 1(st) re-induction given in the FLAG-group may have nullified the initial beneficial effect of L-DNR containing re-induction therapy and led to similar and relatively favorable survival rates in both treatment groups in Germany.
authors.affiliation: Children's Hospital, Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: Children's Hospital, Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Semmler
authors.affiliation: Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: G L
authors.initials: GL
authors.lastname: Kaspers
authors.affiliation: Children's Hospital, Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Children's Hospital, Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012074:Remission Induction; D019233:Retreatment; D015983:Selection Bias; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: C506643:liposomal doxorubicin; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D004317:Doxorubicin; D014740:Vidarabine