title: Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  We evaluated the influence of three different dosages of methotrexate (MTX) during consolidation on the incidence of testicular relapse in children with acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  One thousand one hundred forty-four boys with newly diagnosed ALL, enrolled in three consecutive trials of the Berlin-Frankfurt-Münster group (ALL-BFM 81, 83, 86), were retrospectively evaluated for the influence of MTX on testicular relapse-free interval. The basic treatment design was similar in all trials. No intravenous MTX was used in trial ALL-BFM 81 in the group who received cranial irradiation (CRT) except for a part of standard risk patients. Four courses of intermediate dose MTX (IDM) (0.5 g/m2) were introduced for all patients in trial ALL-BFM 83 (IDM group), which were replaced by high dose MTX (HDM) (5 g/m2) in trial ALL-BFM 86 (HDM group). The media observation time was > 9 years.
  
  
  RESULTS
  The cumulative incidence of isolated testicular relapses was significantly higher in the CRT group as compared to the IDM and HDM groups (6.7% versus 2.5% and 2.3%, p = 0.02 and 0.01). HDM decreased neither the incidence nor the rate of isolated testicular relapses any further. Event-free survival (EFS) for boys was similar between trial ALL-BFM 81 and 86 (64% versus 69%, p = 0.35), but differed significantly between trials ALL-BFM 83 and 86 (61% versus 69%, p = 0.0078).
  
  
  CONCLUSIONS
  The introduction of IDM reduced the incidence of isolated testicular relapses significantly by a factor two, but had no significant influence on overall survival. HDM did not result in a more effective prevention of testicular relapses, but resulted in better systemic control and hence better survival than IDM.
authors.affiliation: Department of Pediatric Hematology/Oncology, University-Children's Hospitals, Hannover Medical School, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dördelmann
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: R
authors.initials: R
authors.lastname: Fengler
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: H
authors.initials: H
authors.lastname: Riehm
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000517:prevention & control* / Q000556:secondary
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate