Survivors of childhood leukemia had an increased risk of infection and infection-related hospitalization and death that persisted for years after completing treatment, a large retrospective cohort study showed.
From discharge to 5 years, leukemia survivors had a 29% to 77% greater risk of infection as compared with age-matched patients with no history of leukemia. The risk of infection remained elevated for 5 years or longer in patients who did not undergo stem-cell transplantation (HSCT), as well as those who did, reported Marie-Claude Pelland-Marcotte, MD, of the Hospital for Sick Children in Toronto, and colleagues.
The findings require additional study to identify potential exposures contributing to the late risk of infection, they stated online in the Journal of Clinical Oncology.
“These results suggest a consistent pattern of an increased number of clinically meaningful infections long after treatment completion for leukemia survivors, even for children who did not undergo HSCT in whom increased susceptibility to infections might not be recognized,” the authors said.
“An understanding of the risks for infection after therapy completion is important because it will guide recommendations for care during this period, including counselling for patients and families and re-immunization practices and medical care for leukemia survivors who present with signs or symptoms of infections,” they added.
The study provided some of the most comprehensive estimates to date of posttreatment and late infections in survivors of pediatric acute leukemia, building on previous studies that focused on infections that required hospitalization or that were based on patient self-report, said Andrew B. Smitherman, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill. Additionally, the study stratified infections according to HSCT status, an outcome not well represented in the literature.
“Understanding that patients’ immune systems may not fully reconstitute for more than a year after completion of acute leukemia therapy, it isn’t surprising to see the increased risk for infection and infection-related hospitalizations, especially in the first year posttherapy,” Smitherman told MedPage Today via email. “Interestingly, though, the increased rates of infections among survivors persisted beyond 5 years posttreatment, a time by which immune reconstitution should have occurred and risk factors such as central lines should be removed.”
“Unfortunately, the authors were not able to obtain information about additional clinical risk factors, such as central lines or continued immunosuppressive therapies,” he continued. “It is possible that many of the infections and hospitalizations in the first year off therapy are related to fevers with a central line in place. By [5 years] posttherapy, the risk for infection-related hospitalization among survivors falls to that seen in the general population.”
Infections are common and a leading cause of mortality during treatment for pediatric acute leukemia. Laboratory studies showed persistent immune dysfunction for months or years after leukemia and chemotherapy, the authors noted, but little information has accumulated regarding infection risk after completion of treatment, particularly among children who did not undergo HSCT.
To address the lack of data, Pelland-Marcotte and colleagues queried an Ontario-based pediatric oncology database to identify children with acute lymphoblastic leukemia or acute myelogenous leukemia and who were alive and relapse free 30 days after hospital discharge from January 1992 to March 15, 2015. Data analysis included 2,204 patients, who were matched with a control group of 11,020 individuals with no history of childhood leukemia. The 13,224-member cohort had a median age of 8 and median follow-up of 7.2 years for both the leukemia survivors and the control group.
Investigators identified a total of 104,410 infections in the entire cohort. Overall, the leukemia survivors had a 51% greater relative risk of infection as compared with the control group (95% CI 1.45-1.57). The risk remained elevated during the first year after discharge (RR 1.77, 95% CI 1.69-1.86), at 1 to 5 years (RR 1.66, 95% CI 1.62-1.71), and beyond 5 years (RR 1.29, 95% CI 1.22-1.36). Excluding patients who did not undergo HSCT yielded a relative risk of 1.29 at 5 years (95% CI 1.23-1.35).
The risk was highest for infections of the blood and central nervous system, associated with relative risks of 1.83 to 18.07 at various time points versus the control group. All infection types occurred significantly more often in leukemia survivors for up to 5 years. Thereafter, all but genitourinary infections continued to be significantly more common in the survivors.
The analysis revealed 56 deaths during the follow-up period. Among patients with cause of death documented by death certificate, leukemia survivors had a relative risk of 149.3 for infection-related death overall and 92.7 after excluding patients without HSCT.
The rate of infection-related hospitalization was significantly higher overall (RR 12.42, P<0.001), up to 1 year (91.81, P<0.001), and up to 5 years (12.85, P<0.001) but not thereafter. A similar pattern was observed in an analysis that excluded the HSCT subgroup.
The study was supported by the Institute for Clinical Evaluative Services/Ontario Ministry of Health and Long-Term Care.
Pelland-Marcotte disclosed support from the Canadian Institutes of Health Research and no relevant relationships with industry.
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Source: MedicalNewsToday.com
