Sequential Treatment with the Anti-CD 20 Antibody Rituximab and CHOP+GCSF Chemotherapy in Patients with Post-Transplant Lymphoproliferative Disorder (PTLD): First Interim Analysis of a Multicenter Phase II Study.

Post-transplant lymphoproliferative disorders (PTLD) are a main causative factor for mortality after organ transplantation. In January 2003 we started a multicenter phase II trial investigating a sequential treatment of the anti-CD 20 antibody rituximab and CHOP + GCSF chemotherapy. 29 patients have been enrolled so far. 14 patients were renal transplant recipients, 5 were heart transplant recipients, 7 were liver transplant recipients, 1 was a combined heart/lung transplant recipient, one was a combined kidney/pancreas transplant recipient and one patient was after bone marrow transplantation. Patients were treated with four weekly doses of 375mg/m² of rituximab as a single therapeutic agent at days 1, 8, 15 and 22. CHOP chemotherapy had been administered at days 50, 72, 94 and 116 and was followed by GCSF starting at day 3 of each chemotherapy cycle. In case of disease progression during administration of rituximab or during the 4-week interval between antibody therapy and CHOP administration the patients directly entered chemotherapy. Histology divided in 21 diffuse large cell-, 2 marginal zone-, 1 Burkitt lymphoma and 3 polymorphic lymphoproliferations. 18 patients had stage III or stage IV disease. Patient age ranged from 16 to 80 years with a median age of 55 years and a mean age of 50.9 years. Time from transplantation to diagnosis divided the patients into two groups. The first group is defined by a median time from transplantation to diagnosis of 6 months (range 1 to 11 months, 11 patients, early PTLD), and a second one is defined by a median time from transplantation to diagnosis of 90 months (range 19 to 204 months, 16 patients, late PTLD). EBV-status was available for 19 patients with 10 EBV-associated PTLD and 9 non-EBV associated PTLD. In August 2005 24 patients were evaluable for treatment response, 25 were evaluable for treatment toxicity. In 84 applied chemotherapy cycles WHO 3°–4° leucopenia occurred in 29 cycles. 9 patients suffered from WHO 3°–4° infections. There were 3 early deaths due to therapy-associated complications. 15 patients (62.5%) achieved complete remission. Partial remission was observed in 5 patients (20.8%). 5 patients experienced progressive disease. With a mean follow up of 10.7 months four patients relapsed. There was no difference in response to rituximab therapy and in response to the sequential treatment of rituximab followed by CHOP chemotherapy for EBV-positive and EBV-negative PTLD. In summary sequential treatment of PTLD with rituximab and CHOP+GCSF is associated with an acceptable toxicity profile and is highly effective with a overall response rate of 83.3%.