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High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center interphase fluorescence in situ hybridization study and review of the literature

Ann Janssens, Nadine Van Roy UGent, Bruce Poppe UGent, Lucien Noens UGent, Jan Philippé UGent, Franki Speleman UGent and Fritz Offner UGent (2012) EUROPEAN JOURNAL OF HAEMATOLOGY. 89(1). p.72-80
abstract
Background : We studied the relation of clonal evolution (CE) in Chronic B-lymphocytic leukemia (CLL) with prognostic factors and the correlation between CE and disease progression and overall survival. Methods : With interphase fluorescence in situ hybridization (FISH) analysis, we looked for 11q22 deletion, 17p13 deletion, and trisomy 12. A second FISH was performed approximately 3 yr after the first one or earlier in case of disease progression. Results : High-risk CE, defined as the acquisition of a new 11q or 17p deletion, was observed in 11.5% (11/95) of patients with CLL. The relative risk of CE was not influenced by CD38 and ZAP-70 expression, mutational status of the immunoglobulin heavy chain gene (IgVH), lymphocyte doubling time, and genomic aberrations observed with the first FISH or by treatment given between the sequential genetic analyses. Patients with high-risk CE had a significant shorter survival time (59 months vs. not reached, P = 0.0367). Multivariate analysis identified CE as the strongest independent prognostic marker regarding survival [hazard ratio (HR) 4.1, P = 0.01]. Clonal fluctuation, defined as disappearance of the 11q or 17p deletion, was seen in 11.5% (11/95) of patients. Most patients lost the high-risk clone after treatment despite persistence of a malignant clone. The disappearance of these genomic aberrations did not ameliorate outcome. A few patients have lost spontaneously a small 17p clone. Conclusion : This study confirms that CE and clonal fluctuation are common phenomena in CLL. CE was not limited to patients with pre-existing adverse prognostic factors. Acquiring high-risk CE was identified as the strongest independent prognostic factor for impaired survival.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
clonal evolution, chronic B-lymphocytic leukemia, clonal fluctuation, karyotype, fluorescence in situ hybridization, CHROMOSOMAL-ABERRATIONS, GENOMIC ABERRATIONS, CD38 EXPRESSION, METAPHASE CYTOGENETICS, KARYOTYPIC EVOLUTION, PROGNOSTIC FACTORS, SCORING SYSTEM, SHORT SURVIVAL, IGV(H) STATUS, CLL
journal title
EUROPEAN JOURNAL OF HAEMATOLOGY
Eur. J. Haematol.
volume
89
issue
1
pages
72 - 80
Web of Science type
Article
Web of Science id
000305280400010
JCR category
HEMATOLOGY
JCR impact factor
2.548 (2012)
JCR rank
34/66 (2012)
JCR quartile
3 (2012)
ISSN
0902-4441
DOI
10.1111/j.1600-0609.2012.01790.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2974417
handle
http://hdl.handle.net/1854/LU-2974417
date created
2012-08-23 14:41:47
date last changed
2012-09-05 11:08:11
@article{2974417,
  abstract     = {Background : We studied the relation of clonal evolution (CE) in Chronic B-lymphocytic leukemia (CLL) with prognostic factors and the correlation between CE and disease progression and overall survival.
Methods : With interphase fluorescence in situ hybridization (FISH) analysis, we looked for 11q22 deletion, 17p13 deletion, and trisomy 12. A second FISH was performed approximately 3 yr after the first one or earlier in case of disease progression.
Results : High-risk CE, defined as the acquisition of a new 11q or 17p deletion, was observed in 11.5\% (11/95) of patients with CLL. The relative risk of CE was not influenced by CD38 and ZAP-70 expression, mutational status of the immunoglobulin heavy chain gene (IgVH), lymphocyte doubling time, and genomic aberrations observed with the first FISH or by treatment given between the sequential genetic analyses. Patients with high-risk CE had a significant shorter survival time (59 months vs. not reached, P = 0.0367). Multivariate analysis identified CE as the strongest independent prognostic marker regarding survival [hazard ratio (HR) 4.1, P = 0.01]. Clonal fluctuation, defined as disappearance of the 11q or 17p deletion, was seen in 11.5\% (11/95) of patients. Most patients lost the high-risk clone after treatment despite persistence of a malignant clone. The disappearance of these genomic aberrations did not ameliorate outcome. A few patients have lost spontaneously a small 17p clone.
Conclusion : This study confirms that CE and clonal fluctuation are common phenomena in CLL. CE was not limited to patients with pre-existing adverse prognostic factors. Acquiring high-risk CE was identified as the strongest independent prognostic factor for impaired survival.},
  author       = {Janssens, Ann and Van Roy, Nadine and Poppe, Bruce and Noens, Lucien and Philipp{\'e}, Jan and Speleman, Franki and Offner, Fritz},
  issn         = {0902-4441},
  journal      = {EUROPEAN JOURNAL OF HAEMATOLOGY},
  keyword      = {clonal evolution,chronic B-lymphocytic leukemia,clonal fluctuation,karyotype,fluorescence in situ hybridization,CHROMOSOMAL-ABERRATIONS,GENOMIC ABERRATIONS,CD38 EXPRESSION,METAPHASE CYTOGENETICS,KARYOTYPIC EVOLUTION,PROGNOSTIC FACTORS,SCORING SYSTEM,SHORT SURVIVAL,IGV(H) STATUS,CLL},
  language     = {eng},
  number       = {1},
  pages        = {72--80},
  title        = {High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center interphase fluorescence in situ hybridization study and review of the literature},
  url          = {http://dx.doi.org/10.1111/j.1600-0609.2012.01790.x},
  volume       = {89},
  year         = {2012},
}

Chicago
Janssens, Ann, Nadine Van Roy, Bruce Poppe, Lucien Noens, Jan Philippé, Franki Speleman, and Fritz Offner. 2012. “High-risk Clonal Evolution in Chronic B-lymphocytic Leukemia: Single-center Interphase Fluorescence in Situ Hybridization Study and Review of the Literature.” European Journal of Haematology 89 (1): 72–80.
APA
Janssens, Ann, Van Roy, N., Poppe, B., Noens, L., Philippé, J., Speleman, F., & Offner, F. (2012). High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center interphase fluorescence in situ hybridization study and review of the literature. EUROPEAN JOURNAL OF HAEMATOLOGY, 89(1), 72–80.
Vancouver
1.
Janssens A, Van Roy N, Poppe B, Noens L, Philippé J, Speleman F, et al. High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center interphase fluorescence in situ hybridization study and review of the literature. EUROPEAN JOURNAL OF HAEMATOLOGY. 2012;89(1):72–80.
MLA
Janssens, Ann, Nadine Van Roy, Bruce Poppe, et al. “High-risk Clonal Evolution in Chronic B-lymphocytic Leukemia: Single-center Interphase Fluorescence in Situ Hybridization Study and Review of the Literature.” EUROPEAN JOURNAL OF HAEMATOLOGY 89.1 (2012): 72–80. Print.