Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström's macroglobulinemia.
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.
Hellmann
A
A
Department of Hematology, University Medical School of Gdanøsk, Poland.
Lewandowski
K
K
Zaucha
J M
JM
Bieniaszewska
M
M
Hałaburda
K
K
Robak
T
T
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D017338:Cladribine