title: Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87.
abstract: OBJECTIVE
  Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria.
  
  
  METHODS
  Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed.
  
  
  RESULTS
  The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 +/- 0.03 and 0.37 +/- 0.03, respectively, with significant differences between the strategic groups (A, 0.18 +/- 0.05 and 0.20 +/- 0.05; B, 0.44 +/- 0.05 and 0.52 +/- 0.05; C, 0.35 +/- 0.09 and 0.42 +/- 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses.
  
  
  CONCLUSIONS
  With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Hagen Graf
authors.initials: HG
authors.lastname: Einsiedel
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hartmann
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Fengler
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Karel
authors.initials: K
authors.lastname: Hählen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Göbel
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001932:Brain Neoplasms / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D013866:Thioguanine / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D013866:Thioguanine; D008727:Methotrexate