Lymphoma risk in children and young adults with inflammatory bowel disease: analysis of a large single-center cohort

Background: Prior studies suggest an increased risk of lymphoma in adults with inflammatory bowel disease (IBD). Cases of lymphoma have also been reported in children with IBD. However, the precise risk of lymphoma in relation to drug exposure has not been ascertained in children.

Methods: We conducted a single-center, retrospective study of 1560 children and young adults with IBD evaluated at Children's Hospital Boston between 1979 and 2008. Of this group, 186 patients were excluded due to incorrect diagnosis, one-time second-opinion visits, or missing hospital records. The remaining 1374 patients had charts reviewed to determine whether lymphoma developed while they were receiving their clinical care at our institution and the duration of exposure to various IBD medications. The rate of lymphoma was calculated in patient-years of exposure for each class of medications utilized in IBD.

Results: Of 1374 patients (741 male; age at diagnosis 12.1 ± 4.0 years; 791 Crohn's disease [CD], 535 ulcerative colitis [UC], 48 IBD unclassified), we identified two patients who developed lymphoma (one Hodgkin, one anaplastic large cell), in 6624 patient-years of follow-up (mean duration follow-up 4.8 years per patient). Both patients were males (ages 12 and 18 years at time of lymphoma onset) and were receiving thiopurines but had not yet received biologics at the time of their cancer diagnosis. They were both treated with chemotherapy and are alive without cancer 32+ and 76+ months since diagnosis. The absolute incidence rate of lymphoma for patients having received thiopurines was 4.5 per 10,000 patient-years compared to the expected rate of 0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.51 (95% confidence interval [CI] 0.74-41.98).

Conclusions: The overall risk of lymphoma in children with IBD is low, with only two cases seen in our hospital over a 30-year period. The lymphoma risk (as estimated by SIR) in children receiving thiopurines is comparable to that reported in studies of adults. While there may be an increased risk of lymphoma in children treated with thiopurines, the risk did not reach statistical significance in this large cohort.