TREATMENT OF CHRONIC LYMPHOCYTIC-LEUKEMIA

The variable course of the disease, the advanced age of most patients and the absence of uniform criteria to evaluate treatment have constituted important setbacks in the therapy of CLL. The advent of clinical staging systems, which allow the identification of patients with different risks and the planning of appropriate therapy, constitutes a major advance. Results of trials based on these staging systems have demonstrated that treatment of patients with CLL in early stage is of no benefit and may even be harmful. By contrast, there is general agreement that patients in advanced stage should be treated. Chlorambucil, either daily or intermittently, and given alone or with corticosteroids, remains the most commonly used drug. Other single agents used in CLL include prednisone, busulphan and cyclophosphamide. Results are often comparable with those observed with chlorambucil alone, although sometimes with more toxicity. The benefit in survival terms of all these drugs remains to be proved. New agents, such as fludarabine, 2-deoxycoformycin and 2-chlorodeoxyadenosine, offer promise. However, the superiority of these drugs over chlorambucil needs to be demonstrated in randomized trials. Most combination therapy regimens have failed to show advantage over chlorambucil with or without prednisone when compared in clinical trials. In a previous randomized trial, the French Co-operative Group on CLL showed a beneficial role for low-dose adriamycin given with cyclophosphamide, vincristine and prednisone (mini-CHOP) in patients with stage C disease. However, these results were obtained in a small series of patients and need to be confirmed. Splenectomy can be considered in patients with autoimmune haemolytic anaemia or thrombocytopenia, with splenic destruction. Radiotherapy, administered either as 32P, total body irradiation, extracorporeal irradiation of blood or thymic irradiation, is effective in a few patients, but severe myelosuppression is a frequent sequel. Splenic irradiation has more often been used when splenectomy was difficult in the case of massive splenomegaly or immune cytopenia. New strategies, including the use of biological response modifiers (interferons, interleukins 2 and 4, erythropoietin, cyclosporine and monoclonal antibodies either alone or conjugated with immunotoxins), are presently under study. So far, only transient effects have been observed. Although complete remission in classical terms is frequently observed with these therapies, clonal remission is a very rare event and cure cannot be achieved. The question as to whether more intensive chemotherapy regimens, including the usage of recombinant haemopoietic growth factors and autologous bone marrow transplantation, and allogeneic bone marrow transplantation, may improve survival in CLL is being actively investigated. However, the morbidity and mortality associated with these procedures makes it necessary to consider their indication carefully and to reserve them for young patients suffering from advanced or chemotherapy-resistant CLL. © 1993 Baillière Tindall. All rights reserved.