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

Abstract

This study evaluates the prognostic significance of genetic abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVHgene 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 unmutatedIGVH 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 unmutatedIGVH 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 IGVHgenes, unmutated IGVH genes, and loss or mutation of thep53 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.

Dic(17;18)(p11.2;p11.2) is a recurring abnormality in chronic lymphocytic leukaemia associated with aggressive disease

“…Our data demonstrated that dic(17;18)(p11.2;p11.2) is a novel recurrent cytogenetic abnormality in CLL associated with early age at diagnosis, accelerated disease progression, and a trend toward more refractory disease. These features are similar to previously published reports of patients with loss of p53 or del(17p13.1) alone, which found these patients to require early therapy, to have poor response to standard purine analog therapy, and have shortened survival (Fenaux et al, 1992;Wattel et al, 1994;Dohner et al, 1995;Cordone et al, 1998;Oscier et al, 2002). Within this subset of del(17p.13.)…”

Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22‐23 deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research

“…The latter hypothesis is intriguing as it would imply a peculiar, still not characterized, B-cell subset as the possible normal counterpart for MCL neoplastic cells. In terms of prognosis, CLL cases with mutated IgH genes have a significantly better prognosis than unmutated genes (Krober et al, 2002;Oscier et al, 2002;Crespo et al, 2003). Mutated MCL cases, however, do not differ in outcome from IgH unmutated cases, an observation confirmed by other recent reports (Camacho et al, 2003;Orchard et al, 2003;Walsh et al, 2003).…”

“…ZNF145 is a frequent breakpoint in acute leukaemias and is a recurrent fusion partner of RAR a in acute promyelocytic leukaemia (Melnick & Licht, 1999). Chromosome 11q21->ter loss is a marker of poor prognosis in CLL Oscier et al, 2002). In this series of MCL, chromosome 11q deletion was not associated with any difference in OS or EFS.…”

A prognostic model for survival in chronic lymphocytic leukaemia based on p53 expression

“…Relationships between p53 dysfunction, CD38 expression and IgV(H) mutation, all adverse prognostic factors, are being explored (Lin et al, 2002). Prognostic schemas based on these molecular abnormalities are likely to be developed and to significantly impact on the therapy of patients with CLL (Oscier et al, 2002). Whether the relatively simple IHC technique will be an accurate enough reflection of the prognostic import of the various pathways leading to abnormal p53 function in CLL will be the subject of future studies.…”