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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1177-1184
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Multivariate analysis of prognostic factors in CLL: clinical
stage, IGVH gene mutational status, and loss or mutation of
the p53 gene are independent prognostic factors
David G. Oscier,
Anne C. Gardiner,
Sarah J. Mould,
Sharron Glide,
Zadie A. Davis,
Rachel E. Ibbotson,
Martin M. Corcoran,
Robert M. Chapman,
Peter W. Thomas,
J. Adrian Copplestone,
Jenny A. Orchard, and
Terry J. Hamblin
From the Department of Haematology, Royal Bournemouth
Hospital, Bournemouth United Kingdom; Dorset Research and Development
Support Unit, Poole Hospital, Poole, United Kingdom; and Department of
Haematology, Derriford Hospital, Plymouth, United Kingdom.
This study evaluates the prognostic significance of genetic
abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVH
gene status in 205 patients with chronic lymphocytic leukemia (B-CLL).
Deletion of chromosome 11q23, absence of a deletion of chromosome
13q14, atypical lymphocyte morphology, and more than 30% CD38
expression are significantly associated with the presence of unmutated
IGVH genes. Advanced stage, male sex, atypical morphology,
more than 30% CD38 expression, trisomy 12, deletion of chromosome
11q23, loss or mutation of the p53 gene, and unmutated
IGVH genes are all poor prognostic factors in a univariate
analysis. However, only 98% or more homology of IGVH genes
to the germline sequence, loss or mutation of the p53 gene,
and clinical stage retain prognostic significance in a multivariate
analysis. The median survival of patients with mutated IGVH
genes, unmutated IGVH genes, and loss or mutation of the
p53 gene regardless of IGVH gene status is 310, 119, and 47 months, respectively. These data should facilitate the
design of new trials for the management of patients presenting with
advanced disease or poor prognosis early stage disease.
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