TY - JOUR
T1 - Lag times between lymphoproliferative disorder and clinical diagnosis of chronic Lymphocytic Leukemia
T2 - A prospective analysis using plasma soluble CD23
AU - Kaaks, Rudolf
AU - Sookthai, Disorn
AU - Łuczyńska, Anna
AU - Oakes, Christopher C.
AU - Becker, Susen
AU - Johnson, Theron
AU - Johansson, Annsofie
AU - Melin, Beatrice
AU - Sjöberg, Klas
AU - Trichopoulos, Dimitrios
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Mattiello, Amalia
AU - Tumino, Rosario
AU - Masala, Giovanna
AU - Agnoli, Claudia
AU - Boeing, Heiner
AU - Aleksandrova, Krasimira
AU - Brennan, Paul
AU - Franceschi, Silvia
AU - Roulland, Sandrine
AU - Casabonne, Delphine
AU - De Sanjose, Silvia
AU - Sánchez, María José
AU - Huerta, José María
AU - Ardanaz, Eva
AU - Sala, Nuria
AU - Overvad, Kim
AU - Tjønneland, Anne
AU - Halkjær, Jytte
AU - Weiderpass, Elisabete
AU - Bueno-De-Mesquita, H. B.
AU - Vermeulen, Roel
AU - Peeters, Petra H.
AU - Vineis, Paolo
AU - Kelly, Rachel S.
AU - Khaw, Kay Tee
AU - Travis, Ruth C.
AU - Key, Timothy J.
AU - Riboli, Elio
AU - Nieters, Alexandra
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Background: Chronic lymphocytic leukemia (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 Prospective Investigation into Cancer cohort, we measured prediagnostic 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% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 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 lymphoproliferative disorder exists before 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.
AB - Background: Chronic lymphocytic leukemia (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 Prospective Investigation into Cancer cohort, we measured prediagnostic 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% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 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 lymphoproliferative disorder exists before 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.
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U2 - 10.1158/1055-9965.EPI-14-1107
DO - 10.1158/1055-9965.EPI-14-1107
M3 - Article
C2 - 25542829
AN - SCOPUS:84927758637
VL - 24
SP - 538
EP - 545
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 3
ER -