Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenstrom's macroglobulinemia

2-Chlorodeoxyadenosine (2-CdA) is a new purine analogue active in indolent lymphoid malignancies. In this retrospective study 22 patients with Waldens trom's macroglobulinemia (MW) were treated with 2-CdA given in 2-h intraven ous infusions. Nine of them were untreated and 13 relapsed or were refracto ry to previous therapeutic modalities with chlorambucil/prednisone (11 pati ents) or COP (2 patients). The patients were given 1-11 (median 4) courses of 2-CdA at the dose of 0.14 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. The courses were repeated every 28-35 d. If severe myelos uppression or infection developed, 2-CdA therapy was stopped until the haem atological parameters increased. The effectiveness of the treatment was eva luated after the 3 cycles and after completion of therapy. None of the pati ents has achieved complete response (CR) after 3 courses of treatment and o nly one (4.5%) has obtained CR after 5 courses. Partial response (PR) was a chieved in 8 (36.4%) patients, giving an overall response rate of 40.9%. Te n further patients (45.4%) responded to the treatment with less than 50% de crease in monoclonal protein (defined as stabilisation). There was no signi ficant difference between the response rate in previously pretreated (38.5% ) and untreated (44.4%) patients (p>0.05). Mean observed decrease in monocl onal protein was 41%. In the group of 9 patients responding to 2-CdA treatm ent mean duration of response was 12 months (range 3-34). Myelosuppression was the most prominent side-effect. Neutropenia was present in 17 (77.3%) a nd thrombocytopenia in 7 (31.8%) patients. In 6 patients myelosuppression w as the reason for treatment discontinuation after 1 or 2 courses without si gnificant therapeutic effect. Seven patients died, including 4 from the res ponding group and all three non-responding patients. Treatment-related thro mbocytopenia and fatal haemorrhage was the course of death in 1 patient. In conclusion, the results of our study show that 2-CdA given in 2-h infusion s is an effective agent in WM and may be given on an outpatient basis. Howe ver, myelosuppression is frequent and the drug must be administered with ca ution.