Immunologic and cytogenetic studies improve prognosis prediction in chronic B-lymphocytic leukemia a multivariate analysis of 24 variables

Juliusson, Gunnar

doi:10.1002/1097-0142(19860801)58:3<688::aid-cncr2820580315>3.0.co;2-o

Cited by 44 publications

(8 citation statements)

References 29 publications

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“…4,26,33,34 We defined a karyotype as complex aberrant if three or more clonal aberrations were present corresponding to the definition in other hematological malignancies and the cited studies in CLL. 4,[33][34][35][36][37][38] Based on FISH data, only 16 cases (3.2%) were identified as complex aberrant karyotype, while 105 cases (21%) showed a complex aberrant karyotype based on CBA. In mean 4.26 aberrations were detected per case (range 3-10).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

et al. 2007

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In CLL data from chromosome banding analysis (CBA) have been scarce due to the low proliferative activity of CLL cells in vitro. We improved the cultivation technique using an immunostimulatory CpG-oligonucleotide DSP30 and IL-2. A total of 506 CLL samples were analysed with CBA and interphase FISH using probes for the detection of trisomy 12, IgH rearrangements and deletions of 6q21, 11q22.3 (ATM), 13q14 (D13S25 and D13S319) and 17p13 (TP53). A total of 500 of 506 (98.8%) cases were successfully stimulated for metaphase generation and are subject to this study. Aberrations were detected in 415 of 500 (83.0%) cases by CBA and in 392 of 500 (78.4%) cases by FISH. CBA detected 832 abnormalities and FISH only 502. Therefore, CBA offers important information in addition to FISH. (1) CLL is characterized mainly by genomic imbalances and reciprocal translocations are rare. (2) A subgroup with complex aberrant karyotype (16.4%) is identified which is associated with an unmutated IgV H status and CD38 expression (P ¼ 0.034 and 0.02, respectively). (3) Additional abnormalities are detectable providing new biological insights into different CLL subclasses revealing a much more heterogeneous pattern of cytogenetic abnormalities as assumed so far based on FISH data only. Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data.

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Section: Discussionmentioning

confidence: 99%

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

et al. 2007

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“…Since complexity is a significant clinical prognostic factor in CLL (11, 17-18, 33), the impact of different mitogens in detecting complex karyotypes was investigated. Given that a case had a complex karyotype in at least one culture, the probabilities of detecting complex (≥3 unrelated abnormalities) abnormal clones were 97.5%, 82.9% and 80.3% in GNKG168+PWM/PMA, GNKG168, and PWM/PMA cultures, respectively (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Enhanced detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide in combination with pokeweed mitogen and phorbol myristate acetate

Muthusamy¹,

Breidenbach²,

Andritsos³

et al. 2011

Cancer Genetics

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Reproducible cytogenetic analysis in CLL has been limited by the inability to obtain reliable metaphase cells for analysis. CpG oligonucleotide and cytokine stimulation have been shown to improve metaphase analysis of CLL cytogenetic abnormalities, but is limited by variability in the cytokine receptor levels, stability and biological activity of the cytokine in culture conditions and high costs associated with these reagents. We report here use of a novel, stable CpG, GNKG168 along with pokeweed mitogen (PWM) and phorbol 12-myristate 13-acetate (PMA) for conventional cytogenetic assessment in CLL. We demonstrate that the combined use of GNKG168+PWM/PMA increased the sensitivity of detection of chromosomal abnormalities compared to PWM/PMA (n=207, odds ratio=2.2, p=0.0002) and GNKG168 (n=219, odds ratio=1.5, p=0.0452). Further, a significant increase in sensitivity to detect complexity ≥3 with GNKG168+PWM/PMA compared to GNKG168 alone (odds ratio 8.0, p=0.0022) or PWM/PMA alone (odds ratio 9.6, p=0.0007) was observed. The trend toward detection of higher complexity was significantly greater with GNKG168+PWM/PMA compared to GNKG168 alone (p=0.0412). The increased sensitivity was mainly attributed to the addition of PWM/PMA with GNKG168 because GNKG168 alone showed no difference in sensitivity for detection of complex abnormalities (p=0.17). Comparison of fluorescence in situ hybridization (FISH) results with karyotypic results showed a high degree of consistency, although some complex karyotypes were present in cases with no adverse FISH abnormality. These studies provide evidence for potential use of GNKG168 in combination with PWM and PMA in karyotypic analysis of CLL patient samples to better identify chromosomal abnormalities for risk stratification.

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“…Since the beginning of 1982, all treatment has been postponed until symptoms (see below) have developed. Patients with only local symptoms were treated throughout the entire period with radiotherapy to the involved region in doses required for symptoms to disappear (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) Gy in 3-4 wk).…”

Section: Treatmentmentioning

confidence: 99%

Prognostic relevance of serum‐markers in relation to histopathology, stage and initial symptoms in advanced low‐grade non‐Hodgkin lymphomas

Martinsson

Glimelius

Hagberg

et al. 1988

European J of Haematology

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The prognostic relevance of 4 different serum markers (deoxythymidine kinase = S-TK, lactic dehydrogenase = S-LDH, S-Haptoglobin and S-Orosomucoid) in relation to histopathology according to the Kiel classification, stage and presence or absence of initial symptoms were investigated in 168 consecutive cases of low-grade non-Hodgkin lymphomas (NHL). All serum markers, as well as the other three parameters, gave prognostic information. Univariate analysis yielded a high predictive value (p < 0.0002) for both S-TK and S-LDH. The best information regarding the probability of survival was, however, obtained from the presence or absence of symptoms from lymphoma manifestations other than those caused by a strictly local tumor mass. Since S-TK and S-LDH correlated well with each other, only the better of them, S-TK, gave information additional to initial symptoms in a multivariate test.

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Immunologic and cytogenetic studies improve prognosis prediction in chronic B-lymphocytic leukemia a multivariate analysis of 24 variables

Cited by 44 publications

References 29 publications

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping

Enhanced detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide in combination with pokeweed mitogen and phorbol myristate acetate

Prognostic relevance of serum‐markers in relation to histopathology, stage and initial symptoms in advanced low‐grade non‐Hodgkin lymphomas

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