Relapsed indolent lymphoid malignancies treated with fludarabine (F) and cyclophosphamide (C) plus sargramostin (GMCSF)

In this phase n trial, patients previously treated for low grade non-Hodgkin's lymphoma (LGNHL) and chronic lymphocytic leukemia (CLL) received a FC regimen with GMCSF support. Efficacy and toxicity were assessed. Symptomatic patients were treated with C 300 mg/m2 IV days I -3 and F 30 mg/m2 IV days 1 -3. Patients were randomized to receive GMCSF 250 mcg/m2SQ starting on day 4 or observation. The treatment was given every 28 days until maximum response or for a total of 6 cycles. Of the 24 patients enrolled, 18 were évaluable with their median age of 62 years old. Of the 12 patients with LGNHL, the mean number of previous treatments was 2.1. Two had stage II disease and 10 had stage IV disease. Of the 6 patients with CLL, the median number of previous treatments was 1.8. Two had stage II disease, 3 had stage III disease and 1 had stage IV disease. For patients with LGNHL, the overall response (OR) was 82% with a 41% complete response (CR) and a 41% partial response (PR). The median duration of response was 12.3 months (range 4-24 months) (one patient was lost to follow-up). The median duration of response for CR was 17 months. For patients with CLL, the OR was 100% with a 16% CR and an 84% PR. The median duration of response was 10.5 months (range 1-26 months). The median duration of response for CR was 24 months. The toxicity of this regimen was mainly hématologie. Due to extended pancytopenia, 5 patients were removed from study and the remaining received a reduced dose regimen of C 250 mg/m2 + F 25 mg/m2. With dose reduction, there were only two episodes of grade 3/4 thrombocytopenia and 5 of grade 3/4 neutropenia. Of the patients not randomized to receive GMCSF, 33% were moved to the GMCSF arm during the course of study. In addition, 1 heavily pre-treated patient developed AML 6 months after this regimen. In conclusion, CF is an effective regimen for treating relapsed indolent lymphoid malignancies. However, a reduced dose regimen was necessary due to severe hématologie toxicities. With dose reduction and GMCSF support, the combination of CF is tolerable and effective.