Anti-CD20 monoclonal antibody (Rituximab) treatment for Epstein-Barr virus-associated, B-cell lymphoproliferative disease in pediatric liver transplant recipients

Abstract

Objectives: Anti-B-cell immunotherapy has been used with success in adults with posttransplant B-cell lymphoproliferative disease (PTLD), but such treatment has rarely been reported in children. We report the outcome of anti-CD20 antibody (rituximab) therapy for Epstein-Barr virus (EBV)-associated PTLD in six pediatric liver transplant recipients.

Methods: In these six patients, PTLD was diagnosed within 2 to 4 months after transplantation. The tumors were classified as monomorphic or polymorphic B-cell infiltrate expressing CD20 antigen and EBV genome. Anti-CD20 therapy was associated with withdrawal of tacrolimus or ciclosporine therapy in all patients. Intravenous rituximab was administered at 375 mg/m2 once a week for 3 to 4 consecutive weeks.

Results: Rituximab treatment was associated with decreased EBV load, disappearance of abnormal serum immunoglobulin concentration, and disappearance of tumoral masses, which occurred 1 to 2.5 months after treatment onset. Despite rituximab therapy, one patient was diagnosed subsequently with a cerebral tumor. Five patients experienced acute liver graft rejection episodes within 10 days to 2.5 months after beginning treatment. In these patients, immunosuppression was reintroduced, but three children experienced fatal chronic rejection, whereas two experienced complete tumor remission. Three children are alive and in complete remission, with normal liver tests, 15 months to 3 years after PTLD onset.

Conclusions: Rituximab therapy is an interesting approach for children with early EBV-associated PTLD after liver transplantation. It does not prevent cerebral localization, and rapid resumption of immunosuppression may be advisable to prevent lethal chronic liver graft rejection.