title: Minimal residual disease-based treatment is adequate for relapse-prone childhood acute lymphoblastic leukemia with an intrachromosomal amplification of chromosome 21: the experience of the ALL-BFM 2000 trial.
abstract: BACKGROUND
  Recently, the UK CCLG and COG reported that an intrachromosomal amplification of chromosome 21 (iAMP21) in acute lymphoblastic leukemia (ALL) loses its adverse prognostic impact with intensified therapy.
  
  
  METHODS
  We evaluated the prognosis of iAMP21 among patients from the ALL-BFM (Berlin-Frankfurt-Münster) 2000 trial with 46 of 2 637 (2%) patients iAMP21+.
  
  
  RESULTS
  8-year event-free-survival (EFS, 64 ± 8% vs. 81 ± 1%, p=0.0026) and cumulative incidence of relapse (CIR, 29 ± 8% vs. 14 ± 1%, p=0.008) of the iAMP21 cases were significantly worse compared with non-iAMP21 patients. Within the MRD low-risk group, iAMP21 cases (n=14) had an inferior 8-year EFS (76 ± 12% vs. 92 ± 1%, p=0.0081), but no increased CIR (10 ± 10% vs. 6 ± 1%, p=0.624). Within the MRD intermediate-risk group, iAMP21 cases (n=27) had a worse 8-year EFS (56 ± 11% vs. 78 ± 2%, p=0.0077) and CIR (44 ± 11% vs. 20 ± 2%, p=0.003) with 6/10 relapses occurring after 2 years.
  
  
  CONCLUSIONS
  Conclusively, we believe that there is no necessity for enrolling all iAMP21 patients into the high-risk arm of ongoing ALL-BFM trials because MRD low-risk patients have a moderate relapse risk under current therapy. Whether the increased relapse risk in MRD intermediate-risk patients can be avoided by late treatment intensification remains to be answered by the AIEOP-BFM ALL 2009 trial randomly using protracted pegylated L-asparaginase during delayed intensification and early maintenance.
authors.affiliation: Department of pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Children's Cancer Research Institute (CCRI), Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Panzer-Grümayer
authors.affiliation: Department of pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Möricke
authors.affiliation: Children's Cancer Research Institute (CCRI), Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: König
authors.affiliation: Children's Cancer Research Institute (CCRI), Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Mecklenbräuker
authors.affiliation: Department of Pediatric Hematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.affiliation: Institute of Pathology, Justus-Liebig-University, Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bradtke
authors.affiliation: Department of Pediatric Hematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.affiliation: Institute of Cell and Molecular Pathology, Medical School of Hannover, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical School of Hannover, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical School of Hannover, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human