Chronic lymphocytic leukemia treatment

Three main question were addressed during this session: 1) Is early treatment better than deferring treatment until necessary for early stage patients?; 2) Is there still a place for chlorambucil (CB) in the treatment of CLL? and 3) Should we consider purine analogues for first line of therapy in CLL? The first question was discussed by Ph. Travade, who presented the long term results from two trials of the French Cooperative Group in previously untreated stage A CLL patients and by Sue Richards who submitted to meta-analysis the data from the American, British, French, and Spanish groups. Consensus was reached to accept that the different randomized trials and the meta-analysis results clearly demonstrate that conventional CB schedules do not prolong survival in these patients. Since deferring therapy until it is required by disease progression to stages B or C does not compromise survival of these patients, therapy should be deferred until progression is observed. It is widely admitted that CB treatment provides relief from symptoms for a large proportion of patients. However, results from different trials presented indicate that at least at conventional schedules, CB is unlikely to prolong survival in CLL. However, Jaksic presented favorable results with high dose (i.e., 10-15 mg/day) continuous CB schedule. The role of purine analogues was discussed by M. Keating and A. Saven, who presented long term results in non-randomized studies with fludarabine (FDB) and 2-chloro-deoxyadenosine (CDA), respectively. In addition the results from two randomized American and French Trials were presented by K. Rai and M. Leporrier. Long term results indicate that purine analogues are active agents in CLL. Both drugs obtain important overall response rates (> 75%) and about 25% complete remissions. Long term results from MD Anderson series indicate that the median progression free interval is 30 months and that, in previously untreated patients, FDB is well tolerated. However, opportunistic infections and autoimmune complications are frequently observed in previously treated patients. Results from the American and French trials confirm that FDB is probably the best single agent in terms of response, since it appears to induce higher response rates than CB and anthracycline containing regimens. No important toxicities were observed in these series including exclusively previously untreated patients. The long term results from MD Anderson show a median survival of 5 years for CLL patients receiving FDB, which is not different to the historical results with other treatment modalities and is confirmed by the present results of the the American and French trials showing no improvement of the overall survival. These results suggest that purine analogues should be included in the list of drugs with proven efficacy in the initial treatment of patients with CLL. Although these drugs produce better responses, they do not cure CLL. For young patients with poor prognosis CLL, future attempts should be made to improve complete remissions at molecular level, which may lead towards significantly increasing the overall survival. Combination of purine analogues with other drugs, autologous transplantation and/or biological response modifiers like monoclonal antibodies or anti-idiotypic vaccines deserve investigation.