How to Choose the Right CLL Treatment

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ASH:

[4900] Choosing the Right Chemotherapy for CLL: Role

of Ex Vivo Apoptotic Drug Response Testing.

G. Bosanquet. Bath Cancer Research, Royal

United Hospital, Bath, Somerset; Department of Medical

Sciences, University of Bath, Bath, Somerset, United

Kingdom

Until recently, choosing chemotherapy for CLL has been

relatively straightforward: chlorambucil followed by

CHOP (cyclophosphamide, doxorubicin, vincristine,

prednisolone). Fludarabine, an excellent drug for many

patients (but not all: Br J Haem 1999;106:71-7), is

now used widely both as a single agent and in

combination.

With an expanding panel of drugs and combinations

possible, chemotherapy options are increasing

enormously. What factors govern choice of

chemotherapy? Initially consideration of precise

diagnosis, stage, concurrent medical conditions and

treatment goal (possible cure, palliation etc) shape

therapy. Choice is based on results from clinical

trials of a cohort of patients who may or may not be

similar in characteristics to the patient in question:

these include cohort probability of response, cohort

life expectancy, cohort short-term and long-term

toxicity and quality of life, plus local or national

guidelines produced on the basis of these results.

Other variables that will affect choice are 'physician

dependent': research interests, knowledge of latest

research and clinical trial results, access to new

drugs, treatment aggressiveness, drug company

marketing, and other less obvious parameters such as

(in the UK's National Health Service) time and

financial constraints.

However, although the results of cohorts in clinical

trials are important, the most relevant response and

life expectancy data are those of the individual

patient. An individual's response to drugs and

combinations of drugs can now be assessed routinely

with the use of ex vivo apoptotic drug response

assays. (These are superior to the MTT assay for CLL

as they are not dependent on the small amount of

cytoplasm available).

The results can augment all other available data and

are, certainly for fludarabine [br J Haem

1999;106:71-7], powerful independent prognostic

factors. Many other variables such as

b2-microglobulin, CD38, p53, bax, etc, have been found

to be prognostic factors but are unlikely to point to

a specific treatment regimen.

On the basis of our ex vivo apoptotic drug response

results, patients have been successfully treated with

a wide variety of therapies. This has included the

identification of high-dose methylprednisolone as an

active agent in a proportion of patients with advanced

CLL [Acta Haematol 1995;93:73-9], and the close

correlation between ex vivo fludarabine or cladribine

results [br J Haematol 1999;106:474-6] and patient

response.

The efficacy of ex vivo apoptotic drug response

testing in relapsed CLL is being tested in a major

international clinical trial run by the UK Medical

Research Council Clinical Trials Committee. A

simplified kit form of the ex vivo drug sensitivity

test that we employ could be used in pathology

laboratories to significantly improve the lot of

individual patients.

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