Cladribine in the treatment of chronic lymphocytic leukemia

Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a nucleoside analog with subs tituted halogen atom at position 2 in its purine ring that makes it resista nt to deamination by adenosine deaminase (ADA), 2-CdA is the drug of choice in the treatment of hairy cell leukemia, but it is also highly active in o ther low grade lymphoid malignancies including chronic lymphocytic Leukemia (CLL). The results of the studies presented so Far have shown that 2-CdA g ives similar complete response (CR) rate and overall response (OR) rate to fludarabine but the influence of both agents on survival times of the patie nts with CLL is still uncertain. CR rate induced with 2-CdA is significantl y higher than in the patients treated with conventional chemotherapy. In re fractory or relapsed patients 2-CdA induces 31 to 68% of overall responses including CR in 4 to 31%. In previously untreated patients overall remissio n rates of about 56-82% have been achieved with 2-CdA alone. When 2-CdA was used as primary therapy the CR rate was also significantly higher and rang ed from 10% to 47%. Patients who received 2-CdA as their initial therapy an d experienced a response lasting at least a year may be successfully treate d subsequently with the same agent. A second response has been achieved in 35 to 100% patients treated with this agent for the second time. Despite th e Fact that 2-CdA gives higher CR and OR rates than conventional chemothera py, it has not been established whether it has any influence on survival ti me, However, cross resistance between 2-CdA and FAMP in CLL patients is evi dent in the majority of studies. Bone marrow suppression with anemia neutro penia and thrombocytopenia are the dose limiting factors for 2-CdA use. The se side effects are pronounced in heavily pretreated patients and after mul tiple courses of therapy. Treatment with this agent also leads to the decre ase of the CD4+/CD8+ ratio for an extensive period of time exceeding 12, ev en up to 24 months. In consequence, infections including opportunistic type , are frequently observed. We suggest, that in patients with CLL, 2-CdA sho uld be used as second line treatment rather than the first line therapy unt il the final results of ongoing randomized clinical trials are available.