Cladribine

Cladribine [2-chlorodeoxyadenosine (2-CdA)] is an adenosine deaminase-resistant purine analog; it is activated within the cell to chlorodeoxyadenosine triphosphate. In vitro, 2-CdA is toxic to lymphocytes. The exact mechanism of action is unknown, but induction of apoptosis appears to be important for its effect on nonreplicating cells (28).

In the initial study of 2-CdA reported by Piro et al. (29), an overall response rate of 22% was seen among 18 patients with CLL. In this study, 2-CdA was administered as a continuous infusion for 7 d at a dose of 0.5-0.2 mg/kg/d. Several other studies confirmed the activity of

2-CdA in CLL, with overall response rates as high as 80% in previously untreated patients and as low as 20% in previously treated patients with more advanced disease (30-35).

In patients refractory to fludarabine, treatment with 2-CdA was not effective. Despite an initial positive report, subsequent studies showed that 2-CdA produced a low response rate in this patient population, and a high incidence of infectious complications was noted (36-38).

2-CdA is usually given as continuous infusion for 5-7 d at a dose of 0.12 mg/kg/d, but similar results have been obtained with 2-h daily infusions for 5-7 d and with subcutaneous and oral administration (31,32). Multiple courses of 2-CdA are required to achieve a maximal response in CLL. The most relevant toxicities are immunosuppression and myelosuppression.

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