Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants

Posttransplant lymphoproliferative disorder (PTLD) has been treated with de creased immunosuppression, antiviral medications, anti-B lymphocyte agents, radiation therapy, and/or chemotherapy. However, a standardized stepwise a pproach to treatment has not been previously evaluated. In the present stud y, 19 consecutive patients presenting to a single institution with newly di agnosed PTLD were treated according to a sequential protocol that consisted of (1) a reduction in immunosuppressive medications plus, if feasible, res ection or definitive radiation therapy of localized disease, (2) interferon -alpha and (3) systemic chemotherapy. Of the 3 patients presenting exclusiv ely with localized disease, two were treated with resection of pulmonary pa renchymal nodules and one was treated with radiation therapy to a paraspino us mass, without evidence of recurrence at a mean follow-up of 31 months (r ange, 8 to 46 months). Sixteen patients presented with PTLD not, amenable t o local therapy, and they were treated daily with 3 x 10(6) units/m(2) subc utaneous interferon-alpha. Total regression of PTLD (defined as disappearan ce of the tumor mass by physical examination or computed tomography scannin g) was found in 8 of 14 patients who received at least 3 weeks of interfero n therapy. Interferon-alpha therapy was continued for 6 to 9 months in the eight patients judged to be responders. None of these patients have relapse d to date with the same neoplastic clone. Two patients, however,developed n ew neoplastic clones. Seven patients received systemic chemotherapy with CH OP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n=1), EPOC H (etoposide, vincristine, and doxorubicin administered as a continuous inf usion, with an intravenous bolus of cyclophosphamide and oral prednisone) ( n=4), or EPOCH followed by DHAP (dexamethasone, cytarabine, and cisplatin) (n=2) after failure of interferon-alpha; five patients had a complete respo nse. Only 1 of the 19 patients died of uncontrolled PTLD. These results sug gest that the majority of solid organ transplant recipients who develop PTL D can be safely and successfully treated using a sequential approach to the rapy.