Thursday, April 03, 2008

CLL: when to start treatment

Most patients with chronic lymphocytic leukaemia present without symptoms or signs; they are identified simply because a blood test has been requested for an unrelated reason. Many of these people never progress or need treatment; however, those who do need treatment usually present in the same way.

Findings of a meta-analysis of seven trials including 2048 early-stage patients randomly allocated either immediate or deferred treatment with chlorambucil (with or without prednisolone) showed no benefit for either treatment group.[120] In a French study,[96] 51% of Binet stage A patients allocated to the deferred group eventually needed treatment and 27% of this group died of a cause related to chronic lymphocytic leukaemia.

Standard management of chronic lymphocytic leukaemia, therefore, includes a period of watchful waiting until features of progression are noted. These signs—of bulk disease, lymphoma-related symptoms, and marrow failure—have been codified by a working group sponsored by the American National Cancer Institute.[121] The document is currently under revision and is unlikely to include recommendations for changes in treatment based on new prognostic markers, but it is likely to recommend new randomised clinical trials with stratification based on such markers. Readers can view the new guidelines here.

With more effective treatments than chlorambucil and better ways of establishing which patients are unlikely to progress, the strategy of watchful waiting should be revisited. Randomised trials of early versus delayed treatment for early-stage patients with poor-risk prognostic markers are planned or underway in Germany, France, the USA, and the UK. In a meta-analysis of ten trials including 2035 advanced-stage patients,[120] addition of anthracycline or a vinca alkyloid to the alkylating agent was not shown to affect outcome.


96 G Dighiero, K Maloum and B Desablens et al., Chlorambucil in indolent chronic lymphocytic leukemia, N Engl J Med 338 (1998), pp. 1506–1514.

120 CLL Trialists' Collaborative Group, Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials, J Natl Cancer Inst 91 (1999), pp. 861–868.

121 BD Cheson, JM Bennett and M Grever et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment, Blood 87 (1996), pp. 4990–4997.


David Arenson said...

Your link to the new guidelines goes to an abstract. The publisher charges for the full text, although they will provide it to patients for free. They'd rather not be pestered by zillions of patients, though, and so patients wishing to read the entire document can download it at no charge from the Treatment Resource Guide at CLL Forum:

Terry Hamblin said...

Thank you, David. I keep forgetting that I have privileged access.