Improving the prevention of cancers in children who have had organ transplants
Organ transplantation is a life-saving treatment for children with organ failure but, after transplant children must take medications that suppress the immune system so that it accepts the organ as the child's own. Unfortunately, these medications significantly increase the risk of developing cancers, especially cancers of the immune cells called lymphomas. Between 2 and 16% of children develop these cancers after transplant, and up to 30% of children with these cancers die from them. These cancers are caused by a common virus, called Epstein Barr virus (EBV), which infects immune cells and turns them into cancer cells. When a child gets infected with EBV for the first time after transplant, the immune system has trouble controlling the infection and there is a high risk of developing lymphoma. These lymphomas are potentially preventable, if the body can control EBV infection. For this reason, we monitor children thought to be at high risk of lymphoma after transplant with a blood test looking for the genetic material of EBV, hoping that we can intervene to prevent lymphoma or diagnose it early when it is easier to treat. Unfortunately, we don't know what part of the blood is most useful to test or how best to interpret the results of these tests as many children get EBV infection and only some develop lymphoma. We have been monitoring EBV in whole blood samples in children transplanted at the Stollery Children's hospital for the last 18 years, and we have gathered information on children that develop lymphomas. We want to review this EBV testing to look for patterns to predict which children will and will not develop lymphomas. We will also perform the EBV test in another part of the blood called plasma, using stored plasma samples, to see if patterns of EBV infection in plasma are more useful than patterns in the whole blood samples we have been using to identify children at high and low risk of lymphoma. High-risk patterns would be used to trigger interventions to get EBV infection under control and potentially prevent lymphoma, while low-risk patterns would identify children who are unlikely to develop lymphoma, so that we can avoid unnecessary testing and treatments in them. If we find promising patterns of EBV infection, we plan to expand to a larger project, involving other hospitals, to ensure that these patterns work well, in large diverse groups of children with transplants, to predict which children are likely and unlikely to develop lymphomas. We hope that the results of our project will inform changes in provincial, national and international guidelines for management of EBV infection and prevention of lymphomas in children with organ transplants, and will help us improve the quality of life for this vulnerable group of children.