Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications

Background and Objective. It has been widely demonstrated that one single 7 -day course continous infusion (c.i.) 2-chlorodeoxyadenosine (2-CdA) at a d ose of 0.1 mg/kg daily is dramatically effective in inducing high and prolo nged complete remission (OR) rates in patients with hairy-cell leukemia (HC L). Row ever, 2-CdA administration often results in severe neutropenia and lymphocytopenia both responsible for the infectious complications observed in these patients. We previously reported preliminary data regarding the ef fectiveness and toxicity of a modified protocol of 2-CdA administration (0. 15 mg/kg 2 hours infusion once a week for 6 courses) in 25 HCL patients. Th is treatment schedule produced a similar overall response rate compared to standard 2-CdA regimen and appeared to be followed by a lower incidence of infectious episodes. In the present study we report response rate and toxic ity of weekly 2CdA administration in a larger cohort of patients and with a longer follow-up. Design and Methods. In a group of HCL patients with a pronounced decrease i n neutrophils count (< 1x10(9)/L), we modified the standard protocol (0.1 m g/kg daily x 7 days c.i.) by administering 2-CdA at a dose of 0.15 mg/kg 2 hours infusion once a week for 6 courses. Thirty HCL patients, 24 males and 6 females with a median age of 56 years(range 37-76), entered into this pr otocol. Seventeen out of 30 patients were at diagnosis while the remaining 13 had been previously treated with alpha-interferon (alpha-IFN) (7), or 2- CdA (4) or deoxycoformycin (DCF) (2). Results. Overall, 22/30 (73%) patients achieved OR and 8 (27%) partial remi ssion (PR) with a median duration of response at the time of writing of 35 months, ranging from 6 to 58 months. Five patients (1 CR and 4 PR) have so far progressed. The treatment was very well tolerated. Five out of 30 patie nts (16%) developed severe neutropenia (neutrophils < 0.5 x 10(9)/L) and on ly in two of them we did register an infectious complication which required treatment with systemic antibiotics and granulocyte colony-stimulating fac tor (G-CSF). Interpretation and Conclusions. In conclusion, we confirm that weekly admin istration of 2-CdA at a dose of 0.15 mg/kg for 6 courses appears to be very effective in HCL inducing a high OR rate, similar to that observed with da ily c.i. administration. CR durability and relapse/progression rates are al so comparable to standard 2-CdA schedule. Moreover this new regimen seems t o be safer in pancytopenic patients, markedly reducing life-threatening inf ectious complications. (C)1999, Ferrata Storti Foundation.