2-Chlorodeoxyadenosine in the treatment of chronic refractory immune thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which autoantibodies, most commonly against either the platelet glycoprotein (GP) IIb/Illa and/or GP Ib/lX complex, result in severe thrombocytopenia. Lasting complete and partial remissions are obtained in about 75% ofpatients with corticosteroids or splenectomy; refractory patients are usually treated with a variety of agents, including gammaglobulin, vinca alkaloids, danazol, colchicine, cyclophosphamide, azathioprine, or staphylococcal immunoadsorption columns.'.* In many patients, these measures are unsuccessful and these patients suffer the consequences of severe thrombocytopenia and chronic immunosuppressive therapy. The nucleoside, 2-chlorodeoxyadenosine (2-CdA), is activated by deoxycytidine kinase. Once incorporated into the nuclear DNA, it is capable of inducing singleand double-stranded breaks in dividing and nondividing cells. Cells rich in deoxycytidine kinase, such as lymphocytes, are the most sensitive to this agent.3 Because 2CdA is active against lymphoid cells and has been used successfully in the treatment of a variety of low-grade lymphoid malignancie~?~ it was thought that it might affect the antiplatelet antibody-producing plasma cell population in patients with chronic refractory ITP. We report our results on the treatment of seven such patients. The patients are summarized in Table I . Seven female patients with a disease duration ranging from 36 to 276 months were treated with one to three cycles of 2-CdA. All patients had failed to respond to high-dose corticosteroids, splenectomy, vincristine, danazol, cyclophosphamide, and intravenous gammaglobulin (IVIgG) therapy. Five patients had also failed other forms of treatment: patient no. I , azathioprine, vinblastine, and anti-D; patient no. 2, vinblastine and a-interferon; patient no. 4, azathioprine, a-interferon, methotrexate, and plasmapheresis; patient no. 5 , colchicine; patient no. 7 , a-interferon, plasmapheresis, and staph A immunosorption. Each cycle of 2-CdA was administered by continuous infusion at a dose ofO. 1 mg/kg/d for 7 days, except for patient no. 2, whose first cycle dose was 0.05 mg/kg/d. Baseline studies consisted of a com-