Management of chronic lymphocytic leukemia

Significant progress has been made in the past two decades in the understanding of immunobiology of CLL and the development of clinical staging systems and identification of other prognostic factors in CLL. A significant advance in the management of CLL has also been made. Now we know when to initiate therapy. We recommend that patients with stage 0 and patients with stages I and II associated with good prognostic features such as absence of disease-related symptoms, long lymphocyte doubling time, nondiffuse bone marrow infiltration, and low tumor load not be treated; they should be followed at 2- to 6-month intervals. We recommend initiation of therapy for patients with stages I and II, associated with poor prognostic features such as presence of disease-related symptoms, short lymphocyte doubling time, diffuse bone marrow infiltration, and high tumor load and for patients with stages III and IV. However, we still do not know what constitutes the optimal therapy for the disease. In one large randomized study, the response rate as well as survival superiority of CHOP (with low-dose Adriamycin) over COP in previously untreated patients with stage C disease was observed. In another large randomized study, only a response rate advantage of CHOP (with standard dose Adriamycin) over chlorambucil and prednisone (in previously untreated patients with stages B and C) was seen. No randomized studies have compared CHOP versus chlorambucil and prednisone in patients with stages III and IV or stage C. At present, our recommendation for the treatment of patients with advanced disease is chlorambucil and prednisone therapy. New drugs under clinical trials for CLL include (1) deoxycoformycin, (2) 2-chlorodeoxyadenosine, and (3) fludarabine monophosphate. Both deoxycoformycin and 2-chlorodeoxyadenosine have been shown to have some activity in previously treated CLL patients with advanced disease. The effectiveness of these agents, however, has not been tested yet in untreated patients with advanced disease. Fludarabine monophosphate, on the other hand, has been shown to be very effective in both previously treated and untreated patients with advanced disease. Allogeneic bone marrow transplantation recently has been found to be of benefit in some patients (37 to 46 years) in a preliminary study; this therapeutic procedure should be tested further in a larger population of younger patients (less than 50 years) with advanced CLL. New agents such as lymphokines (interferons and IL-2) and monoclonal antibodies have been investigated for their efficacy and found to be minimally effective in previously treated patients with advanced disease.(ABSTRACT TRUNCATED AT 400 WORDS)