Fludarabine based combinations are highly effective as first-line or salvage treatment in patients with Waldenstrom macroglobulinemia

Treatment with single-agent chemotherapy or rituximab (R) is safe and moderately effective for patients with Waldenstrom macroglobulinemia (WM). We analyzed the efficacy and toxicity of fludarabine (F)-combinations. Twenty-nine treatment episodes were administered to 27 patients, including FC (F 25 mg/m= 3 neutropenia and infections complicated 28% and 3% of cycles, respectively. Responses were achieved in 26 cases (90%), one complete, 23 partial, and two minor. The median progression-free survival was 43.1 months, and at a median follow-up of 66.5 months the actuarial 5- and 10-year overall survival-rates were 88% and 75%, respectively. All 10 previously untreated patients responded (one CR, nine PR), and were alive at a median follow-up of 50 (6-106) months. Three heavily pretreated patients subsequently developed AML/MDS (one fatal) at 56, 61, and 91 months post F-based treatment. F-combination therapy is highly active in WM, both untreated and alkylator-refractory. However, a possible contribution to the cumulative risk of treatment-related MDS/AML requires ongoing monitoring.