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.
Subject(s)
Anti-Infective Agents/therapeutic use , Bacterial Infections/drug therapy , Mycoses/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Adolescent , Bacterial Infections/complications , Bacterial Infections/mortality , Child , Child, Preschool , Down Syndrome/genetics , Female , Humans , Infant , Male , Multivariate Analysis , Mycoses/complications , Mycoses/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Retrospective Studies , Risk Factors , Survival Rate , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Pancreatitis/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Acute Disease , Adolescent , Adult , Asparaginase/adverse effects , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Risk Factors , Young AdultSubject(s)
Nervous System Neoplasms/diagnosis , Neuroblastoma/diagnosis , Sympathetic Nervous System/pathology , Female , Fetal Diseases/diagnosis , Fetal Diseases/genetics , Fetal Diseases/therapy , Humans , Infant, Newborn , Male , Nervous System Neoplasms/genetics , Nervous System Neoplasms/therapy , Neuroblastoma/genetics , Neuroblastoma/secondary , Neuroblastoma/therapy , Practice Guidelines as Topic , Prenatal Diagnosis , PrognosisABSTRACT
Childhood obesity is a growing problem that has serious implications for future generations. The cause is multifactorial, with contributions from genetics and the environment. Management needs to be targeted at the population as a whole, with improved education and strategies to improve lifestyle and behaviour. Medication and surgery play a very small role in management, for use in exceptional circumstances. Only by empowering individuals and families to change will there be any impact on this epidemic.
