title: Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia.
abstract: BACKGROUND
  In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications.
  
  
  METHODS
  We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 and ALL-2000 protocols. Fifty-five TRDs were identified among the 1,645 ALL-92 patients and 33 among the 1,090 ALL-2000 patients.
  
  
  RESULTS
  There was no significant difference in the incidence of TRDs between the two protocols (3.4% vs. 3.2%). Five patients died before initiation of therapy (0.2%), and the overall subsequent risk of induction death and death in first complete remission (CR1) was 1.2% and 1.8%, respectively. Infections were the major cause of death comprising 72% of all cases including 9 deaths from Pseudomonas aeruginosa and 11 deaths from fungal infections. Other causes of death included bleeding or thrombosis (eight patients), tumour burden related toxicities (seven patients) and organ toxicity (seven patients). Female gender (hazard ratio (HR): 2.2, 95% confidence interval (95% CI): 1.4-3.4), high white blood cell count (≥ 200 × 10(9) /L) at diagnosis (HR: 3.5, 95% CI: 1.7-7.1), T-cell disease (HR: 1.9, 95% CI: 1.01-3.7), Down syndrome (HR: 7.3, 95% CI: 3.6-14.9) and haematopoietic stem cell transplantation in CR1 (HR: 8.0, 95% CI: 3.3-19.5) were identified as independent risk factors for TRD.
  
  
  CONCLUSIONS
  Several TRDs were potentially preventable and future efforts should be directed towards patients at risk.
authors.affiliation: Department of Pediatrics, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. bendik.lund@ntnu.no
authors.forename: Bendik
authors.initials: B
authors.lastname: Lund
authors.forename: Ann
authors.initials: A
authors.lastname: Åsberg
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Jukka
authors.initials: J
authors.lastname: Kanerva
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderhäll
authors.forename: Ólafur Gisli
authors.initials: ÓG
authors.lastname: Jónsson
authors.forename: Stian
authors.initials: S
authors.lastname: Lydersen
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D009894:Opportunistic Infections / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology / Q000401:mortality; D047368:Tumor Burden