Towards chemotherapy-free treatment of lymphoid tumours in children with solid organ transplants

Organ transplantation provides lifesaving treatment for thousands of children worldwide each year. Nevertheless, children with transplants are at risk of several serious complications.

One of these is post-transplant lymphoproliferative disorder – PTLD. PTLD is when B-lymphocytes, the type of white blood cell that produces antibodies, grow out of control, sometimes developing into a form of cancer (lymphoma). In most children, PTLD is caused by Epstein Barr Virus (the glandular fever virus) which infects B-lymphocytes. These infected cells are normally kept under control by the immune system but the immune suppressing drugs that transplant recipients must take to prevent the immune system from rejecting the transplanted organ also diminish this control and the B-lymphocytes accumulate abnormally.

The treatment of PTLD is difficult because doctors must balance treating the PTLD against the risk of potentially devastating organ rejection and the toxic side effects of chemotherapy. As a result, the outcomes for children with PTLD are not as good as for other children with lymphoma. Unfortunately, there is little knowledge about how PTLD develops from B-lymphocytes to help doctors treat PTLD patients, or to suggest effective alternatives to chemotherapy.

Dr Chris Bacon, Dr Simon Bomken and Professor Vikki Rand are conducting research that aims to fill that gap in understanding. The research group has teamed up with colleagues in Spain to read the genetic code of PTLD cells to learn more about the genetic changes that drive this disease. We will also characterise the cells that make up the local environment in which the PTLD cells proliferate, to understand how they promote the development of PTLD tumours. Through these experiments we will determine new ways to improve outcomes for children with PTLD, by aiding clinical decision making and identifying opportunities to develop new drugs, or repurpose existing drugs, as alternatives to chemotherapy.