Mycophenolate mofetil-induced neutropenia in liver transplantation

Mycophenolate mofetil (MMF) is a potent, safe immunosuppressive agent for rescue therapy of acute and chronic rejection in orthotopic liver transplant recipients. It helps to reduce the serious toxic side effects of calcineurin inhibitors (CNIs). The side effects of MMF, such as bone marrow toxicity, have been reported. Herein we report four patients who underwent liver transplantation and developed neutropenia while receiving MMF.

Between April 2002 and October 2003, we performed 24 liver transplants in 25 patients. Eighteen patients were given MMF for the following reasons: renal failure in nine (50%); treatment of acute rejection in three (16.6%); primary prophylaxis of rejection in five (27.7%); and CNI withdrawal in one (5.5%).

Of the 18 patients treated with MMF, there were 11 men (61.1%) and seven women (38.8%), with an overall mean age of 55.5 years. This therapy was ceased in four patients due to neutropenia (22%). Discontinuation of MMF was followed by a rapid and spontaneous rise in neutrophils in two patients. Granulocyte colony stimulating factor (GCSF) was administered to one patient and in another a bone marrow biopsy was performed due to persistent anemia, leukopenia, and thrombocytopenia. The mean time from starting MMF to the development of neutropenia was 4 months. Only the third patient showed elevated levels of MMF.

MMF is a potent immunosuppressive agent in liver transplantation. However, because serious hematologic toxicity has been reported, we recommend caution in administration and careful monitoring of blood levels.