Infections in Survivors of Childhood Leukemia

Infections are a frequent and often severe complication during treatment for pediatric leukemia, but little is known about infections that occur after treatment completion. The aim of this dissertation was to describe the epidemiology of infections in pediatric leukemia survivors using three distinct research projects. First, a systematic review was performed to estimate the incidence of infections in survivors of acute lymphoblastic and acute myeloid leukemia. The 28 included studies suggested that infections were a frequent complication in survivors of childhood leukemia, especially for children whose treatment included hematopoietic stem cell transplant (HSCT). However, results were limited by the paucity of studies and participants. Second, we aimed to estimate the rate of infection in survivors of pediatric leukemia compared to matched children from the general population. A retrospective population-based cohort study was performed using administrative data housed at ICES . The rate of infections was elevated after treatment completion compared with controls overall (relative rate, 1.51; 95% confidence interval [CI], 1.45 to 1.57) and at less than 1 year, 1 to 4.99 years and 5 or more years from the index date (30 days after treatment completion). Infection-related mortality was also significantly increased in pediatric leukemia survivors, both in the entire cohort and when the analysis was restricted to children whose treatment did not include HSCT. Third, we performed a retrospective cohort study to compare the risk of severe infection (life-threatening or fatal) after therapy completion between children with leukemia compared to children with other cancer types. The cumulative incidence (95% CI) of severe infections at 3 years was 0.58% (0.40-0.81%) overall, 0.70% (0.40-1.2%) in leukemia survivors and 0.51% (0.32-0.79%) in survivors of other cancers. The risk of severe infection was not statistically different in leukemia survivors compared to other cancer types (adjusted hazard ratio: 1.40, 95% CI: 0.69-2.85, p=0.351), even after adjustment for age, sex, and exposure to HSCT. This dissertation found that infections are a clinically relevant problem in leukemia survivors. Future research should identify those at highest risk of infection following treatment completion, who might benefit from clinical interventions to prevent infections and minimize their impact.Ph.D