Long-Term Risk of Hospitalization Among Five-Year Survivors of Childhood Leukemia in the Nordic Countries

Abstract

Background: Adverse effects from childhood leukemia treatment may persist or present years after cure from cancer. We provide a comprehensive evaluation of subsequent hospitalization in five-year survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).

Methods: In the Adult Life after Childhood Cancer in Scandinavia Study, we identified 4003 five-year survivors diagnosed with childhood leukemia 1970-2008 in Denmark, Sweden, Iceland, and Finland. Survivors and 129 828 population comparisons were followed for first-time nonpsychiatric hospitalizations for 120 disease categories in the hospital registries. Standardized hospitalization rate ratios and absolute excess rates were calculated. All statistical tests were two-sided.

Results: Survivors of ALL (n = 3391), AML (n = 389), and CML (n = 92) had an increased overall hospitalization rate compared with population comparisons. The rate ratio for any hospitalization was 1.95 (95% confidence interval [CI] = 1.83 to 2.07) in ALL, 3.09 (95% CI = 2.53 to 3.65) in AML, and 4.51 (95% CI = 3.03 to 6.00) in CML survivors and remained increased even 20 years from leukemia diagnosis. Corresponding absolute excess rates per 1000 person-years were 28.48 (95% CI = 24.96 to 32.00), 62.75 (95% CI = 46.00 to 79.50), and 105.31 (95% CI = 60.90 to 149.72).

Conclusion: Leukemia survivors have an increased rate of hospitalization for medical conditions. We provide novel insight into the relative and absolute rate of hospitalization for 120 disease categories in survivors of ALL, AML, and CML, which are likely to be informative for both survivors and healthcare providers.

Figure 1.

Flow diagram showing exclusions from the study cohorts. Index date is defined as the date of the cancer diagnosis of the corresponding patient. Study follow-up ended on date of death, date of emigration, or end of study (Iceland: December 31, 2008; Sweden: December 31, 2009; Denmark: October 31, 2010; Finland: December 31, 2012), whichever occurred first. Start date of the respective national hospital registries: Sweden, stepwise inclusion of counties in 1968–1987 and nationwide since 1987; Finland, 1969; Denmark, 1977; Iceland, 1999.

Figure 2.

Standardized hospitalization rate ratio for five-year survivors of acute lymphoblastic leukemia, by time period since leukemia diagnosis, and stratified by decade of leukemia diagnosis. Error bars indicate 95% confidence intervals (CI). Decades of leukemia diagnosis = 1970–1979, 1980–1989, and 1990–1999.

Figure 3.

Risk of hospitalization in each of 12 main diagnostic groups by type of leukemia. Results are shown for (A) acute lymphoblastic leukemia, (B) acute myeloid leukemia, and (C) chronic myeloid leukemia. Each person can be hospitalized for more than one of specific disease categories within each main diagnostic group (please see Methods for details). Obs. = observed number of hospitalizations; RR = standardized hospitalization rate ratio. CI = confidence interval.

Figure 4.

Cumulative incidence for any hospitalization in leukemia survivors and matched population comparisons. Results are shown for (A) acute lymphoblastic leukemia (ALL), (B) acute myeloid leukemia (AML), and (C) chronic myeloid leukemia (CML).