Atypical lymphocyte morphology: an adverse prognostic factor for disease progression in stage A CLL independent of trisomy 12

Oscier, David; Matutes, Estella; Copplestone, Adrian; Pickering, Ruth; Chapman, Robert M.; Gillingham, R.; Catovsky, Daniel; Hamblin, Terry J.

doi:10.1046/j.1365-2141.1997.3263141.x

Cited by 91 publications

(43 citation statements)

References 31 publications

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“…In this cohort of strictly classified CLL patients the rates of spontaneous apoptosis and response to fludarabine and cladribine showed wide variation and no significant difference was apparent between patients with typical or atypical CLL (Table 2). Atypical CLL is clinically more aggressive than typical CLL, 17 however, the results presented here imply that atypical CLL lymphocytes are not more resistant to the in vitro induction of apoptosis. When the effect of prior treatment was examined, 13 patients who had completed therapy more that 6 months before assessment (but with significant disease present) were compared with 35 previously untreated patients (one patient receiving treatment immediately prior to the assay was excluded from analyses); analyses showed no statistically significant difference (Mann-Whitney U test) between the two groups for either spontaneous or drug-induced response (Table 3A).…”

Section: Drug Sensitivity Assaycontrasting

confidence: 53%

“…In this report, strict morphological and immunophenotypic criteria have been used to define the patient population and inclusion has been restricted to CLL only. 16 A recent report suggested that atypical CLL was more likely to progress clinically than typical CLL, 17 implying that some fundamental difference exists between these two subtypes of disease. The present belief that CLL arises through a defect in the apoptotic pathway raises the question as to whether typical and atypical CLL show similar apoptotic responses, and led to the further classification of patients in this report as typical and atypical CLL.…”

Section: Introductionmentioning

confidence: 99%

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In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues – correlation with clinical course

et al. 1998

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Samples from 51 chronic lymphocytic leukaemia (CLL) patients (42 typical, nine atypical) were assessed for in vitro response to fludarabine and cladribine (2-CdA) using the flow cytometric terminal deoxynucleotidyl transferase (TdT) assay. No difference was demonstrated between the in vitro response of typical and atypical CLL and previous treatment did not result in a more apoptosis resistant phenotype. The assay could not distinguish those patients who required subsequent treatment from those whose disease remained stable, and universal cross-resistance/sensitivity to the two purine analogues was demonstrated. The assay's potential for use in the rapid assessment of in vivo response to purine analogue therapy in CLL was limited; correctly predicting the clinical outcome of 10/12 patients to treatment but failing to predict progression in two p53 deficient patients. The level of bcl-2 in the clonal lymphocytes did not influence the in vitro, spontaneous or drug-induced, apoptosis.

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Section: Drug Sensitivity Assaycontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues – correlation with clinical course

et al. 1998

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“…[1][2][3][4][5] Early in the 1990s, conventional cytogenetic analysis (CCA) demonstrated that approximately 50% of CLL cases may show clonal aberrations and that specific cytogenetic patterns have independent prognostic significance. 6 A complex karyotype was associated with an inferior outcome and patients with trisomy 12 in their karyotype were shown to survive less than patients with 13qÀ or with normal karyotype.…”

Section: Introductionmentioning

confidence: 99%

“…7 Later on, fluorescence in situ hybridization (FISH) techniques demonstrated that up to 80% of the cases may carry a chromosomal defect in interphase cells, 8 giving the opportunity to better analyze the correlations of cytogenetic lesions and clinicobiological features. Convincing evidence was provided that: (a) 13q deletion occurring as an isolated chromosome lesion is associated with typical morphology and a benign clinical course; 4,5 (b) patients with trisomy 12 usually display an excess of large lymphocytes identifying the CLL mixed-cell-type variant of the FAB classification; 9,10 (c) 11q22-23 and 17p13 deletion may identify specific clinicopathological subsets of CLL having an inferior outcome. [11][12][13] A hierarchical cytogenetic classification was finally defined as having a strong correlation with the clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

et al. 2003

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Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13qÀ), 69 cases with 'intermediate risk'(1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11qÀ or 17pÀ). Six out of 13 cases with 6qÀ showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; 420% CD38 þ cells were seen in 5/6 cases. IGVH mutational status revealed 498% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6qÀ showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38 þ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6qÀ group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6qÀ anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6qÀ), showing that the 6qÀ chromosome maintained its prognostic significance at multivariate analysis (P ¼ 0.02) along with stage (P ¼ 0.01). We conclude that CLL with 6qÀ is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

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“…However, they do not distinguish which patients in early stages of the disease will progress. Other prognostic parameters, e.g., short lymphocyte doubling time and/or diffuse bone marrow infiltration are known risk factors for progressive disease in early-stage CLL [2,3]. Although patients lacking these features have a low risk for disease progression, 10-15% of such cases will still progress within 5 years of diagnosis, emphasizing the need for additional prognostic factors in early CLL [3,4].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL

Odero¹,

Soto²,

Matutes³

et al. 2001

Cancer Genetics and Cytogenetics

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Cytogenetic analysis is useful in the diagnosis and to assess prognosis of B-cell chronic lymphocytic leukemia (B-CLL). However, successful cytogenetics by standard techniques has been hindered by the low in vitro mitotic activity of the malignant B-cell population. Fluorescence in situ hybridization (FISH) has become a useful tool, but it does not provide an overall view of the aberrations. To overcome this hurdle, two DNA-based techniques have been tested in the present study: comparative genomic hybridization (CGH) and amplotyping by arbitrarily primed PCR (AP-PCR). Comparative genomic hybridization resolution depends upon the 400-bands of the human standard karyotype. AP-PCR allows detection of allelic losses and gains in tumor cells by PCR fingerprinting, thus its resolution is at the molecular level. Both techniques were performed in 23 patients with stage A B-CLL at diagnosis. The results were compared with FISH. The sensitivity of AP-PCR was greater than CGH (62% vs 43%). The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% (15/19) of patients in whom G-banding was not informative, providing a global view of the aberrations in a sole experiment. This study shows that combining these two methods with FISH, makes possible a more precise genetic characterization of patients with B-CLL.

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Atypical lymphocyte morphology: an adverse prognostic factor for disease progression in stage A CLL independent of trisomy 12

Cited by 91 publications

References 31 publications

In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues – correlation with clinical course

In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues – correlation with clinical course

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL

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