Present status of purine analogs in the therapy of chronic lymphocytic leukemias

Chronic lymphocytic leukemia (CLL) is considered an incurable disease and therefore the management is palliative and more disease-related symptoms directed. Recently, the high activity of nucleoside analogs as fludarabine (FAMP), 2-chlorodeoxyadenosine (2-CDA) and 2-deoxycoformycin (DCF) in low-grade NHLs has caused a new reawakening interest in CLL concerning new treatment strategies, the biology and prognostic factors of this disease. Predominantly FAMP has widely been studied in CLL with impressive remission rates of 30-70%, including some complete remission (CR) in refractory or relapsed CLL. In previously untreated patients, the remission rate is about 80% with a CR rate of up to 60%. These results open new treatment strategies, even with a curative intention such as high-dose chemotherapy combined with autologous stem cell support or allogeneic stem cell transplantation. The clinical experience with 2-CDA in CLL is limited, but the preliminary results suggest a similar efficacy as FAMP, whereas DCF seems to be less effective. The major treatment-related morbidity is due to myelo- and immunosuppression by long-lasting T cell depletion, which may facilitate a greater susceptibility of infections including those with opportunistic organisms as herpes simplex or herpes zoster, cytomegalovirus, Pneumocystis carinii, mycobacteria, listeriosis, candida and aspergillus in pretreated patients. However, in previously untreated patients no increased incidence of infections has been reported compared with other schedules. Whether FAMP treated patients have any advantage for overall or progression-free survival has to be answered by ongoing randomized trials. Presently, the position of FAMP and 2-CDA as two extremely active single agents in CLL is that of second-line therapy. Their appropriate indication in the first-line strategy of CLL has, however, still to be defined by clinical studies in progress.