2-chloro-2'-deoxyadenosine: clinical applications in hematology

The anticancer drug 2-chloro-2'-deoxyadenosine (CdA) belongs to the family of purine nucleoside analogs. CdA is exquisitely cytotoxic both to the dividing and to the non-dividing lymphocyte, which supports its use in lymphoproliferative disorders of low-grade malignancy. Indeed, the best clinical results with CdA are achieved in hairy-cell leukemia, in chronic lymphocytic leukemia, in Waldenström's macroglobulinemia and in low-grade malignant lymphoma. Most patients with hairy-cell leukemia achieve a complete response with a single course of CdA. However, the disease is not eradicated and a fraction of complete responders will eventually relapse. In chronic lymphocytic leukemia and in malignant lymphoma, complete or partial responses can be achieved in approximately 40% of previously treated patients, even after classical chemotherapy has failed. However, few responses sustain beyond 1 to 2 years, while longer unmaintained responses may be obtained in Waldenström's macroglobulinemia. More responses (70-80%) are achieved in patients with chronic lymphoproliferative disorders treated de novo with CdA but their impact on survival remains to be established. More than 10 years after its first use in clinical practice, late adverse consequences of the severe and sustained immunosuppression induced by CdA have not been reported but should still be closely monitored.