Weekly Administration of 2-Chlorodeoxyadenosine in Patients With Hairy-Cell Leukemia: A New Treatment Schedule Effective and Safer in Preventing Infectious Complications

To the Editor:

The treatment options for hairy-cell leukemia (HCL) have increased rapidly in the last 10 to 15 years. HCL patients currently can benefit from several agents such as α-interferon (α-IFN), deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (2-CdA). Despite complete remission (CR) rates ranging from 5% to 10% with α-IFN^1,2 to 70% to 80% with DCF^3,4 and 2-CdA,5-7 the prognosis for a patient with HCL has improved dramatically with an overall survival superior to 10 years with any of these treatments. Given these considerable results, it is extremely important to reduce in these patients any risk of toxic deaths usually related to severe infectious complications more frequently observed after treatment with 2-CdA. In fact, it is well known that this agent, either administered as a continuous infusion (c.i.) for 7 days or as a 2-hour infusion for 5 days, frequently induces severe neutropenia and CD4 lymphocytopenia, both leading to infectious complications in about one third of neutropenic patients.8 

Because 2-CdA toxicity could be partly related to the administration schedule of the drug, in the attempt to reduce the number and severity of complications, particularly crucial in those patients showing severe pancytopenia at the onset of the treatment, we investigated the effectiveness and toxicity of 2-CdA administered with a different regimen. In a selected group of HCL patients, showing a more pronounced impairment of peripheral blood values (hemoglobin [Hb] level <10 g/dL; neutrophil count <1 × 10 g/dL; platelet count <100 × 10 g/dL), 2-CdA was administered at a dose of 0.15 mg/kg once a week for 6 courses.

Twenty-five HCL patients, 22 males and 3 females with a median age of 56 years (range 37 to 71), entered this protocol. Twelve of 25 patients were enrolled at the time of diagnosis while the remaining 13 were previously treated. Patients characteristics and results are summarized in Table 1. Overall, 19 of 25 (76%) patients achieved CR and 6 of 25 (24%) partial remission (PR). All CRs were documented by routine histology and by immunohistochemical studies. Responses were independent of previous therapy and disease duration. The time to response was similar to that observed with daily 2-CdA administration and in responsive patients HC cells were already undetectable in the bone marrow at about 1 month after the end of treatment. The median disease-free survival was 14.7 months, ranging from 3 to 31 months. Only two patients, both achieving partial response, have progressed.

The treatment was very well tolerated and is noteworthy that only 4 of 25 patients (16%) developed severe neutropenia (neutrophil count <0.5 × 10 g/dL). Infectious complications, requiring the use of systemic antibiotics and granulocyte colony-stimulating factor, were observed only in 2 of these neutropenic patients. Therefore, only 8% (2 of 25) of the patients treated with this protocol suffered from infectious episodes.

The rationale for our study was twofold: (1) to confirm the response rate of standard 2-CdA administration schedules; (2) to reduce the infectious complications rate potentially cause of early deaths in HCL patients. The data presented here show that weekly administration of 2-CdA was as effective as the standard protocols in inducing high complete response rates (76%) in HCL patients. Moreover, even if the patients were already pancytopenic at the beginning of the treatment, we observed a markedly reduced number of both severe neutropenic and infectious episodes (16% and 8%, respectively). These results are very important considering that 2-CdA–induced neutropenia can result in life-threatening infections in patients that could otherwise potentially be cured from the disease or at least face a relatively prolonged survival.

In conclusion, given the effectiveness and safety observed, we propose this new schedule of 2-CdA administration as the treatment of choice in neutropenic HCL patients.