TREATMENT OF WALDENSTROMS MACROGLOBULINEMIA RESISTANT TO STANDARD THERAPY WITH 2-CHLORODEOXYADENOSINE - IDENTIFICATION OF PROGNOSTIC FACTORS

Background: Few effective treatments are available for patients with W aldenstrom's macroglobulinemia that is resistant to standard therapies . We assessed the activity of 2-chlorodeoxyadenosine (2CdA) in patient s with resistant macroglobulinemia in order to identify those most lik ely to benefit. Patients and methods: 2-chlorodeoxyadenosine was given to 46 consecutive patients with Waldenstrom's macroglobulinemia resis tant to a combination of an alkylating agent and a glucocorticoid. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump t hrough a central venous catheter. Responding patients were followed wi thout further therapy. Results: Twenty of 46 patients responded to 2Cd A therapy (43%; 95 CI; 29 to 60%) with a significantly higher frequenc y of benefit among patients with disease relapsing off therapy (78%) o r with primary resistant disease within the first year (57%) than in t hose with later phases of disease (22%). The median survival after tre atment was 28 months and the median progression-free survival of respo nding patients was 12 months. The longest survival was measured in pat ients with primary refractory disease (projected median 36 months) and the shortest in those with disease in refractory relapse (median 13 m onths). Conclusion: 2-Chlorodeoxyadenosine is active against macroglob ulinemic lymphoma resistant to standard regimens and most effective in patients with disease relapsing off treatment or during the first yea r of primary refractory disease. Little benefit was observed among pat ients with later phases of resistant disease who should receive altern ative treatments.