Prospective study of sequential reduction in immunosuppression, interferon alpha-2b, and chemotherapy for posttransplantation lymphoproliferative disorder

Background. Several interventions can cure posttransplant lymphoproliferative disease (PTLD); a sequential approach is Usual, starting with reduction in immunosuppressives (RI). The efficacy of RI remains poorly defined, particularly in adults. We assessed an algorithm starting with a defined course of RI in all patients, escalating to interferon (IFN) alpha2b, and finally to chemotherapy, in a prospective multicenter phase II study of adult solid organ transplant recipients. The design predated rituximab. Methods. Reduction in immunosuppressives: cyclosporine or tacrolimus reduction by 50% for 2 weeks; a further 50% reduction for I week if not in complete remission (CR). Intravenous acyclovir was given for the duration of all RI. Patients with less than CR, or any rejection, resumed immunosuppressives and proceeded to IFN 3 MIU/m(2)/day for up to 3 months; if less than CR, ProMACE-CytaBOM chemotherapy. Results. Twenty patients were registered over 60 months; 16 patients with biopsy-proven PTLD were eligible (13 heart, 3 kidney recipients). Median age was 47 (24-75) years. Reduction in immunosuppressives resulted in only 1 of 16 partial responses (12.5%), no CR. Progressive disease occurred in 8 of 16 (50%) and 6 of 16 (38%) experienced rejection. Only I of 13 (7%) patients achieved durable CR with IFN. Seven eligible patients received ProMACE-CytaBOM chemotherapy, five of seven (67%) achieving CR, four of five durable beyond 2 years. Conclusions. Reduction in immunosuppressives produced no CR, progressive disease and rejection were frequent; response to IFN was rare. A strong case can be made for adding rituximab to R1 as initial therapy. Chemotherapy resulted in 57% durable CR, data that are relevant for the up to two thirds of PTLD patients who are refractory to rituximab.