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Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23.

Kaaks, Rudolf; Sookthai, Disorn; Luczynska, Anna; Oakes, Christopher Charles; Becker, Susen; Johnson, Theron; Johansson, Ann Sofie; Melin, Beatrice; Sjöberg, Klas LU and Trichopoulos, Dimitrios, et al. (2015) In Cancer Epidemiology Biomarkers & Prevention 24(3). p.538-545
Abstract
Background:CLL is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. Methods:Within the European EPIC cohort, we measured pre-diagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. Results: In a very large proportion of CLL patients plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% CI (0.90, 1.00)] for CLL diagnosed within 0.1-2.7 years after blood measurement, 0.90 [0.86-0.95] for diagnosis within 2.8-7.3 years, and 0.76... (More)
Background:CLL is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. Methods:Within the European EPIC cohort, we measured pre-diagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. Results: In a very large proportion of CLL patients plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% CI (0.90, 1.00)] for CLL diagnosed within 0.1-2.7 years after blood measurement, 0.90 [0.86-0.95] for diagnosis within 2.8-7.3 years, and 0.76 [0.65-0.86] for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. Conclusions:Our findings provide unique documentation for the very long latency times during which measurable B-cell lympho-proliferative disorder exists prior to the clinical manifestation of CLL. Impact:Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag-times indicate a time frame within which an early detection of CLL would be theoretically possible. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
24
issue
3
pages
538 - 545
publisher
American Association for Cancer Research
external identifiers
  • pmid:25542829
  • wos:000351953100009
  • scopus:84927758637
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-14-1107
language
English
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yes
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7daab618-42bc-432c-952b-26622aac924f (old id 4905557)
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http://www.ncbi.nlm.nih.gov/pubmed/25542829?dopt=Abstract
date added to LUP
2015-01-07 14:00:49
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2017-10-01 03:12:06
@article{7daab618-42bc-432c-952b-26622aac924f,
  abstract     = {Background:CLL is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. Methods:Within the European EPIC cohort, we measured pre-diagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. Results: In a very large proportion of CLL patients plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% CI (0.90, 1.00)] for CLL diagnosed within 0.1-2.7 years after blood measurement, 0.90 [0.86-0.95] for diagnosis within 2.8-7.3 years, and 0.76 [0.65-0.86] for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. Conclusions:Our findings provide unique documentation for the very long latency times during which measurable B-cell lympho-proliferative disorder exists prior to the clinical manifestation of CLL. Impact:Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag-times indicate a time frame within which an early detection of CLL would be theoretically possible.},
  author       = {Kaaks, Rudolf and Sookthai, Disorn and Luczynska, Anna and Oakes, Christopher Charles and Becker, Susen and Johnson, Theron and Johansson, Ann Sofie and Melin, Beatrice and Sjöberg, Klas and Trichopoulos, Dimitrios and Trichopoulou, Antonia and Lagiou, Pagona and Mattiello, Amalia and Tumino, Rosario and Masala, Giovanna and Agnoli, Claudia and Boeing, Heiner and Aleksandrova, Krasimira and Brennan, Paul and Franceschi, Silvia and Roulland, Sandrine and Casabonne, Delphine and de Sanjose, Silvia and Sanchez, Maria-Jose and Huerta, Jose-Maria and Ardanaz, Eva and Sala, Nuria and Overvad, Kim and Tjonneland, Anne and Halkjær, Jytte and Weiderpass, Elisabete and Bueno-de-Mesquita, H Bas and Vermeulen, Roel and Peeters, Petra H and Vineis, Paolo and Kelly, Rachel S and Khaw, Kay-Tee and Travis, Ruth C and Key, Timothy J and Riboli, Elio and Nieters, Alexandra},
  issn         = {1538-7755},
  language     = {eng},
  number       = {3},
  pages        = {538--545},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23.},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-14-1107},
  volume       = {24},
  year         = {2015},
}