Blood Journal
Leading the way in experimental and clinical research in hematology

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

  1. David O’Connor1,
  2. Jessica Bate2,
  3. Rachel Wade3,
  4. Rachel Clack3,
  5. Sunita Dhir4,
  6. Rachael Hough5,
  7. Ajay Vora6,
  8. Nick Goulden7, and
  9. Sujith Samarasinghe7
  1. 1Imperial College London, London, United Kingdom;
  2. 2Institute of Child Health, University College London, United Kingdom;
  3. 3Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;
  4. 4Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom;
  5. 5University College Hospital, London, United Kingdom;
  6. 6Sheffield Children’s Hospital, Sheffield, United Kingdom; and
  7. 7Great Ormond Street Hospital, London, United Kingdom

Key Points

  • Infection is the major cause of treatment-related mortality in pediatric acute lymphoblastic leukemia and is greatest during the induction phase.

  • Children with Down syndrome are at high risk for infection-related mortality throughout all treatment phases, including the low-intensity maintenance phase.

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.

  • Submitted March 7, 2014.
  • Accepted May 25, 2014.
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