Treatment of Posttransplant Lymphoproliferative Disorder Presenting as Protracted Infectious Mononucleosis with Rituximab

Two young children who received living related-donor orthotopic liver transplantation for congenital biliary atresia developed persistent and progressive symptoms of fever, hepatosplenomegaly, upper airway obstruction, swollen eyes and face, malaise and cervical lymphadenopathy consistent with infectious mononucleosis within one year post-transplantation. Significant anemia, elevated liver transaminases and hypergammaglobulinaemia were observed. Serological assays did not detect any antibodies to Epstein-Barr virus (EBV) pre-transplantation indicating seronegative status. Both patients showed recent seroconversion to EBV (viral capsid antigen IgM and IgG positive but EBV nuclear antigen negative) at the peak of the clinical symptoms. The diagnosis of primary EBV-driven posttransplant lymphoproliferative disorder (PTLD) was established. Lowering or withdrawal of tacrolimus for a period of 2–3 weeks did not lead to any discernible clinical improvement. Both children were treated with four weekly doses of rituximab of 375 mg/m2/dose. They developed infusion reaction of fever, vomiting and unstable blood pressure within half hour of first dose of rituximab requiring stoppage of the drug administration. Subsequent doses were tolerated much better without adverse events. Clinical improvement was gradually observed over the next few weeks with resolution of fever, upper airway obstruction, decreasing liver transaminases and improvement of general condition. Complete resolution of infectious mononucleosis and normalization of hematological and biochemical parameters was achieved over a period of 6 months. No recurrence of PTLD was observed up to one year after treatment with rituximab.