Successful treatment of 2 patients with B-cell post-transplant lymphoproliferative disorders with rituximab

Rituximab (anti-CD20) has recently been successfully used in the treatment of patients with post-transplant lymphoproliferative disorders (PTLD). We report one patient who had a dramatic overnight response to this regimen and another with bulky aggressive lymphorna in which this drug helped stabilize disease to control severe tumor lysis syndrome, subsequently allowing multiagent chemotherapy to be safely given. Patient #1 is a 38 year old male S/P orthotopic cardiac transplantation 5/89 for idiopathic dilated cardiomyopathy, who developed stage IIIA polymorphous PTLD 7/99, with abdominal pain, cervical and axillary nodes up to 2 cm, and a 3.5 cm retroperitoneal mass. Treatment consisted of discontinuation of cyclosporine A and azathioprine with substitution of Prednisone 10 mg and oral cyclophosphamide 1 mg/kg daily, along with acyclovir. On the same day, rituximab 375 mg/m² was given, with a subsequent severe allergic reaction which responded to slowing the infusion. Within 12 hours, he had dramatic reduction in the peripheral lymphadenopathy and abdominal pain. EBV genomes were elevated to 4000 copies/ng peripheral blood DNA (nl 0-400), and fell to 0 following the first treatment. Complete remission (CR) occurred following 4 rituximab treatments. He remains in CR 14 months later, on low dose cyclosporine A immunosuppression. Patient #2 was a 62 year old male S/P orthotopic cardiac transplant 11/89 for ischémie cardiomyopathy. He presented 9/99 with stage IVA Burkitt's-like PTLD with a bulky retroperitoneal mass causing renal obstruction, lymphomatous bleeding gastric ulcers, bladder and bone involvement, paraneoplastic sideroblastic anemia, renal failure, and spontaneous tumor lysis syndrome. He was treated with hydration, alkalinization. allopurinol, ureteral stent, continuous venovenous hemodialysis, discontinuation of chronic cyclosporine A and azathioprine with substitution of oral cyclophosphamide 1 mg/kg/day, acyclovir, and 8 doses of rituximab 375 mg/m² IV. There was a slight decrease in the size of abdominal mass following the first rituximab dose, with resolution of the tumor lysis syndrome, allowing hyperCVAD (pulse cyclophosphamide, adriamycin, vincristine, decadron) to be initiated 2 weeks later. He achieved a CR which was sustained until he died of an arrhythmia 6 months following diagnosis of PTLD. Rituximab offers an effective new addition to the current treatment of PTLD, even in patients with advanced bulky disease.