2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom's macroglobulinemia

Treatment for Waldenstrom's macroglobulinemia (WM) has usually been reserved for symptomatic patients and has included alkylating agent-steroid combinations and, more recently, nucleoside analogues. We now describe our experience with 2-chlorodeoxyadenosine (2-CdA) alone and in combination at our center. We treated 90 consecutive, previously untreated patients with symptomatic WM using either 2-CdA alone or in combination with other agents including prednisone (pred), cyclophosphamide (Cy), and rituximab (Rit) as follows: January 1991 to December 1992 - 2-CdA 0.1 mg/kg by continuous infusion (CI) over 24 hours for days (16 patients); December 1992 to December 1995 - 2-CdA 0.1 mg/kg CI over 24 hours for 7 days plus pred 60 mg/m² orally daily for 7 days (20 patients); July 1996 to March 1998 - 2-CdA 1.5 mg/m² by subcutaneous injection (SC) every 8 hours for 7 days plus Cy 40 mg/m² orally twice daily for 7 days (37 patients); August 1999 to December 2001 - 2-CdA 1.5 mg/m² SC every 8 hours for 7 days plus Cy 40 mg/m² orally twice daily for 7 days plus Rit 375 mg/m² by intravenous infusion (IV) weekly for 4 weeks (17 patients). For nearly all patients, a second course was repeated after at least 6 weeks. Responding patients were monitored without further treatment until relapse. Overall response (complete [CR] + partial response [PR]) was 94% for 2-CdA alone, 60% for 2-CdA/pred, 84% for 2-CdA/Cy, and 94% for 2-CdA/Cy/Rit. Median overall survival is 73 months for 2-CdA, 41 months for 2-CdA/pred, and has not been reached for 2-CdA/Cy or 2-CdA/Cy/Rit. Cause-specific survival for 2-CdA/pred is 78 months and has not been reached for all other programs. The only poor prognostic factor for cause-specific survival was hemoglobin < 9 g/dL. 2-CdA regimens provide excellent response rates and improve cause-specific survival, with minimal treatment and little toxicity. These observations support the potential role of 2-CdA regimens as the treatment of choice for previously untreated WM.