Objective: to assess the potential risk of cancer and its risk factors in paediatric transplant recipients.
Design: analytical retrospective longitudinal observational study conducted in the framework of the US Transplant Cancer Match (TCM) Study.
Setting: the data were retrieved from the Scientific Registry of Transplant Recipients (SRTR) database, which has records of all solid organ transplantations performed in patients aged less than 18 years in 16 states of the United States between 1987 and 2011.
Study population: out of 18 150 transplantations in patients aged less than 18 years included in the TCM Study (45% of all solid organ transplantations in the United States), 17 958 were selected, corresponding to 16 732 individuals, and 1% were excluded because the recipients did not belong to any of the included race categories.
Risk factor assessment: the unit of analysis was transplantation of a solid organ. The authors assessed demographic and clinical patient characteristics, the indication for transplantation, patient EBV serology status before transplantation and the race of transplant recipients.
Outcome measurement: the primary endpoint was the development of cancer classified according to the third edition of the Classification of Diseases for Oncology. At-risk time spanned from the transplant date or the start of cancer registry coverage to the first of the following events: death, graft failure, retransplantation, loss to followup or end of cancer registry coverage. Followup extended beyond 18 years of age. The authors summarised the results by means of standardised incidence ratios (SIRs) calculated by the direct method (dividing observed cancer counts among recipients by expected counts based on the general population rates) for total cancer and for specific types of cancer. Since non-Hodgkin lymphoma (NHL) was the most frequent type of cancer, the authors also calculated specific SIRs for NHL by age, transplanted organ, time to development of cancer and EBV status. The authors performed multivariate Cox regression to examine associations with potential risk factors.
Main results: of the 18 150 selected transplant recipients, 17 958 were included in the analysis (1% excluded). Of the total, 54.3% were male, 54.5% were aged less than 9 years, and 53.8% were Caucasian, and the median duration of followup was 4 years (interquartile range [IQR]: 1-7 years). The EBV status was known in 48% of the patients, of who 46% were seronegative. A total of 392 cancers were diagnosed, with a SIR of 212.95% (95% confidence interval [95 CI]: 188 to 238). The most frequent type was NHL (SIR: 18.5%; 95 CI: 13 to 26), with an increased incidence relative to the general population independently of age, years since transplantation and EBV status. The risk factors for NHL identified in the multivariate analysis were first year after transplant, EBV seronegative status, transplant type (heart, lung and intestine), and duration of immunosuppression, although there were no significant differences based on age, sex or race.
Conclusion: paediatric transplant recipients are at higher risk of developing cancer compared to the general population. The most frequent cancer type was non-Hodgkin lymphoma, with a higher risk in the first year post transplant, in recipients susceptible to primary infection by EBV and in intestine transplant recipients.
Conflicts of interest: one of the authors is employed by Grail (a company dedicated to the early detection of cancer), the rest declared no conflicts of interest.
Funding source: none noted.