title: Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003.
abstract: Although infection is the major cause of treatment-related mortality (TRM) in childhood acute lymphoblastic leukemia, factors associated with infection-related mortality (IRM) are poorly understood. To address this, we report an analysis of all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was 2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249 trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight percent of cases were associated with bacterial infection (64% Gram-negative) and 20% with fungal infection. Down syndrome was the most significant risk factor for IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04), as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24-3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly, patients with Down syndrome were at significantly higher risk for IRM during maintenance (P = .048). Our results confirm Down syndrome as a major risk factor for IRM. Enhanced supportive care and prophylactic antibiotics should be considered in high-risk patient groups and during periods of increased risk. This study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119.
authors.affiliation: Imperial College London, London, United Kingdom;
authors.forename: David
authors.initials: D
authors.lastname: O'Connor
authors.affiliation: Institute of Child Health, University College London, United Kingdom;
authors.forename: Jessica
authors.initials: J
authors.lastname: Bate
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;
authors.forename: Rachel
authors.initials: R
authors.lastname: Wade
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;
authors.forename: Rachel
authors.initials: R
authors.lastname: Clack
authors.affiliation: Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom;
authors.forename: Sunita
authors.initials: S
authors.lastname: Dhir
authors.affiliation: University College Hospital, London, United Kingdom;
authors.forename: Rachael
authors.initials: R
authors.lastname: Hough
authors.affiliation: Sheffield Children's Hospital, Sheffield, United Kingdom; and.
authors.forename: Ajay
authors.initials: A
authors.lastname: Vora
authors.affiliation: Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Goulden
authors.affiliation: Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
mesh_terms: D000293:Adolescent; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009181:Mycoses / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents