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

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Abstract
2‐Chlorodeoxyadenosine (2‐CdA) is a new purine analogue active in indolent lymphoid malignancies. In this retrospective study 22 patients with Waldenström's macroglobulinemia (MW) were treated with 2‐CdA given in 2‐h intravenous infusions. Nine of them were untreated and 13 relapsed or were refractory to previous therapeutic modalities with chlorambucil/prednisone (11 patients) 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 myelosuppression or infection developed, 2‐CdA therapy was stopped until the haematological parameters increased. The effectiveness of the treatment was evaluated after the 3 cycles and after completion of therapy. None of the patients has achieved complete response (CR) after 3 courses of treatment and only one (4.5%) has obtained CR after 5 courses. Partial response (PR) was achieved in 8 (36.4%) patients, giving an overall response rate of 40.9%. Ten further patients (45.4%) responded to the treatment with less than 50% decrease in monoclonal protein (defined as stabilisation). There was no significant difference between the response rate in previously pretreated (38.5%) and untreated (44.4%) patients (p >0.05). Mean observed decrease in monoclonal protein was 41%. In the group of 9 patients responding to 2‐CdA treatment mean duration of response was 12 months (range 3–34). Myelosuppression was the most prominent side‐effect. Neutropenia was present in 17 (77.3%) and thrombocytopenia in 7 (31.8%) patients. In 6 patients myelosuppression was the reason for treatment discontinuation after 1 or 2 courses without significant therapeutic effect. Seven patients died, including 4 from the responding group and all three non‐responding patients. Treatment‐related thrombocytopenia 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 infusions is an effective agent in WM and may be given on an outpatient basis. However, myelosuppression is frequent and the drug must be administered with caution.