By Marilynn Larkin
NEW YORK (Reuters Health) – Pediatric organ transplant patients are at increased risk for many cancers, especially non-Hodgkin’s lymphoma (NHL) - possibly due to Epstein-Barr viral (EBV) transmission in the donor organ, researchers say.
Dr. Eric Engels of the National Cancer Institute in Rockville, Maryland and colleagues analyzed data on 16,732 individuals who received 17,958 transplants from 1987 to 2011, when they were under age 18.
Fifty-four percent of recipients were male, 54% were white, 24% were Hispanic, 18% were African American, and 5% were Asian/Pacific Islander. About half had data on pretransplant EBV serostatus; about half of those were EBV-negative.
The median year of transplantation was 2001, and 44% of transplanted organs were kidney, 32% liver, 21% heart and/or lung, and 1% intestine. After transplantation, 392 cancers were diagnosed over a median of four years of follow-up.
As reported in Pediatrics, online April 26, the overall cancer incidence among recipients was more than 19 times higher than in the general population (standardized incidence ratios = 19.1).
NHL incidence was 212 times higher (SIR = 212); Hodgkin’s lymphoma, 19 times higher (SIR = 18.5); and leukemia, four times higher (SIR = 4).
NHL risk was highest during the first year after transplantation among recipients under age five at transplant (SIR = 313); those seronegative for EBV (SIR = 446); and among intestine recipients (SIR = 1280).
Analyses showed that seronegative EBV status, the first year after transplantation, intestine transplantation, and induction immunosuppression were independently associated with a higher incidence of NHL.
Across all cancer types, the largest increase in incidence was for myeloma (SIR = 229), based on three cases.
Pediatric recipients also had a higher incidence of cancers of the kidney (SIR = 15.5), thyroid (SIR = 6.00), liver (SIR = 30.8), testis (SIR = 3.98), soft tissue (SIR = 4.45), ovary (SIR = 7.40), bladder (SIR = 28.1), and vulva (SIR = 17.4), also based on small numbers of cases.
Dr. Engels told Reuters Health by email, “Children and adolescents who receive a solid organ transplant have an extraordinarily high risk for NHL, more than 200 times higher than seen in the general population.”
“All transplant recipients are at increased risk of NHL due to the use of immunosuppressive medications,” he noted, “but this risk is greatly elevated in children who do not have pre-existing immunity to EBV and who acquire the infection for the first time after transplantation.”
Editorialist Dr. Daniel Wechsler of Duke University Medical Center in Durham, North Carolina, told Reuters Health, “While it has been previously known that adults who receive solid organ transplants are at a higher risk for developing cancer, this is the first study to systematically address this issue in pediatric patients.”
“One of the scary things about the authors’ findings was that the average follow-up was only four years, and the oldest patient was only 38 years old,” he said by email. “Since tumors in adulthood are generally more common, it is possible that these patients might be at an even higher risk as they get older.”
“Another important issue is the potential impact of EBV on development of lymphomas and other blood cell-derived tumors,” he noted. “It is known that immune suppression can lead to reactivation of EBV infection, and it is possible that early recognition and treatment of EBV infection might be able to reduce the chances of developing lymphomas.”
“As more and more immune based therapies – checkpoint inhibitors, CAR-T cells and others – come into clinical practice, we need to be mindful of the fact that even though they may have incredible antitumor effects in part because of their effects on the immune system, these therapies could perturb or mess up the immune system to allow other tumors to develop,” Dr. Wechsler cautioned.
“The field of immunotherapy is still in its infancy,” he concluded, “and we are continuing to learn about the power of these treatments, but also their not-insignificant side effects.”
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