title: Cerebral venous sinus thrombosis in children with acute lymphoblastic leukemia carrying the MTHFR TT677 genotype and further prothrombotic risk factors.
abstract: BACKGROUND
  The present study was designed to prospectively evaluate the role of prothrombotic risk factors in leukemic children treated according to the ALL-BFM 90/95 study protocols with respect to the onset of cerebral venous sinus thrombosis.
  
  
  METHODS
  317 consecutive leukemic children aged 6 months to 18 years were enrolled in this study. 288 of the 317 patients were available for thrombosis-free survival analysis.
  
  
  RESULTS
  In 17 (5.9%) of these 288 patients cerebral venous sinus thrombosis occurred. The overall event-free survival of thrombosis in the central nervous system in patients with at least one prothrombotic defect (n = 12) was significantly reduced compared with patients without a prothrombotic defect (p < 0.0001). 15 patients showed acute clinical symptoms at onset of cerebral venous sinus thrombosis, two were asymptomatic. Three of the 17 patients affected (17.6%) died directly associated with the thrombotic event during induction therapy, the remaining 14 patients did not show prolonged clinical symptoms.
  
  
  CONCLUSIONS
  Prothrombotic risk factors should be included in a screening program in ALL children treated according to the BFM study protocols. Further prospective studies are recommended to establish adequate prophylactic anticoagulant treatment during ALL (BFM) polychemotherapy.
authors.affiliation: Pediatric Hematology/Oncology, University Hospitals Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wermes
authors.forename: G
authors.initials: G
authors.lastname: Fleischhack
authors.forename: R
authors.initials: R
authors.lastname: Junker
authors.forename: R
authors.initials: R
authors.lastname: Schobess
authors.forename: D
authors.initials: D
authors.lastname: Schwabe
authors.forename: K W
authors.initials: KW
authors.lastname: Sykora
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D007020:Hypoprothrombinemias / Q000235:genetics*; D015994:Incidence; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D012851:Sinus Thrombosis, Intracranial / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D015996:Survival Rate
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)