Post-transplantation malignant tumors and the challenges of immunosuppressive therapy in transplanted patients developing lymphoma. Mycophenolic acid as a possibility]

The increasing frequency of malignant tumors developing during chronic immunosuppression is an important determinant of the long-term survival of organ transplanted patients. This problem can be solved only if we are aware of the special characteristics concerning our patients. The incidence and frequency of tumors occurring in kidney transplant recipients differ from those of the Hungarian population. The increased tumor risk resulting from chronic renal failure, increasing age of prospective kidney recipients and, in addition, the increasing frequency of tumors diagnosed in the early post-transplantation period emphasize the importance of regular oncological screening of patients on the waiting list. Early diagnosis and treatment of tumors and precancerous conditions are equally important in transplanted patients as well, and the tumor risk could be decreased by applying low dose immunosuppression and the preferential usage of immunosuppressive drugs with an oncologically favorable effect. The prognosis of post-transplantation tumors is poor, as they respond poorly to therapy. Lymphomas are of great importance because of their frequency. Different immunosuppressive regimens represent varying degrees of risk in lymphoma development. This risk is lower in the case of mycophenolic acid. The composition of immunosuppression is a major factor in treatment; an oncologically ideal compound would prevent organ rejection and, at the same time, would not counteract oncological therapy. We have shown that mycophenolic acid inhibits the proliferation of human B-cell non-Hodgkin lymphomas and induces apoptosis by activating the intrinsic pathway, both in vitro and in vivo. The favorable properties of mycophenolic acid suggest that it can provide the necessary immunoprotection for the transplanted organ and, given its anti-lymphoma effects, it may also prove useful in the therapy of lymphoma patients. It may also be helpful in the treatment of "traditional" lymphomas of the non-transplanted population, where the major cause of therapeutical failure is the development of apoptosis resistance. Mycophenolic acid, combined with other chemotherapeutical drugs, may enhance apoptosis in lymphoma cells. Our promising experimental results provide a basis for further, clinical studies.