Achieving Optimal Outcomes in Chronic Lymphocytic Leukaemia

Hamblin, T.J.
March 2001
Drugs;Mar2001, Vol. 61 Issue 5, p593
Academic Journal
Chronic lymphocytic leukaemia (CLL) is a disease of late middle age and older. The majority of patients are diagnosed because of a lymphocytosis of at least 5 x 10/L on an incidental blood count. It needs to be distinguished from mantle cell lymphoma and splenic marginal zone lymphoma by lymphocyte markers. The immunophenotype of CLL is sparse surface immunoglobulin, CD5+, CD19+, CD23+, CD79b-, and FMC7-. The disease is staged according to the presence of lymphadenopathy and/or splenomegaly and the features of bone marrow suppression. Most patients have an early stage of disease when diagnosed and perhaps 50% will never progress. This group of patients have a normal life expectancy and do not require treatment beyond reassurance. Progression involves an increasing white cell count, enlarging lymph nodes and spleen, anaemia and thrombocytopenia. Complications of progression include autoimmune haemolytic anaemia and thrombocytopenia, immunodeficiency, and the development of a more aggressive lymphoma. A range of prognostic factors is available to predict progression, but most haematologists rely on close observation of the patient. Intermittent chlorambucil remains the first choice treatment for the majority of patients. Combination chemotherapy offers no advantage. Intravenous fludarabine is probably more effective than chlorambucil, but no trial has yet shown a survival advantage for using it first rather than as a salvage treatment in patients not responding to chlorambucil. It is at least 40 times as expensive as chlorambucil. Cladribine may be as effective as fludarabine, although it has been used less and is even more expensive. Patients who relapse after chlorambucil should be offered retreatment with the same agent and if refractory should be switched to fludarabine, which may also be offered for retreatment on relapse. For patients refractory to both drugs, a variety of options are available. High dose corticosteroids, high dose chlorambucil, CHOP (cyclophosphamide, prednisolone, vincristine and doxorubicin), anti-CD52, anti-CD20 and a range of experimental drugs which are being evaluated in clinical trials. Younger patients should be offered the chance of treatment with curative intent, preferably in the context of a clinical trial. Autologous stem cell transplantation after achieving a remission with fludarabine has relative safety and may produce molecular complete remissions. Only time will tell whether some of these patients are cured but it seems unlikely. Standard allogeneic bone marrow transplant is probably too hazardous for most patients, but non-myeloablative regimens hold out the hope of invoking a graft-versus-leukaemia effect without a high tumour-related mortality. Trials of immunotherapy are exciting options for a few patients in specialised centres.



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