Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23.
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 di...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2014
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| _version_ | 1826256430157529088 |
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| author | Kaaks, R Sookthai, D Luczynska, A Oakes, C Becker, S Johnson, T Johansson, A Melin, B Sjöberg, K Trichopoulos, D Trichopoulou, A Lagiou, P Mattiello, A Tumino, R Masala, G Agnoli, C Boeing, H Aleksandrova, K Brennan, P Franceschi, S Roulland, S Casabonne, D de Sanjose, S Sanchez, M Huerta, J |
| author_facet | Kaaks, R Sookthai, D Luczynska, A Oakes, C Becker, S Johnson, T Johansson, A Melin, B Sjöberg, K Trichopoulos, D Trichopoulou, A Lagiou, P Mattiello, A Tumino, R Masala, G Agnoli, C Boeing, H Aleksandrova, K Brennan, P Franceschi, S Roulland, S Casabonne, D de Sanjose, S Sanchez, M Huerta, J |
| author_sort | Kaaks, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:02:09Z |
| format | Journal article |
| id | oxford-uuid:00229531-5f97-4c63-80e7-d1fc47e60a47 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:02:09Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:00229531-5f97-4c63-80e7-d1fc47e60a472022-03-26T08:28:10ZLag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:00229531-5f97-4c63-80e7-d1fc47e60a47EnglishSymplectic Elements at Oxford2014Kaaks, RSookthai, DLuczynska, AOakes, CBecker, SJohnson, TJohansson, AMelin, BSjöberg, KTrichopoulos, DTrichopoulou, ALagiou, PMattiello, ATumino, RMasala, GAgnoli, CBoeing, HAleksandrova, KBrennan, PFranceschi, SRoulland, SCasabonne, Dde Sanjose, SSanchez, MHuerta, JBackground: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. |
| spellingShingle | Kaaks, R Sookthai, D Luczynska, A Oakes, C Becker, S Johnson, T Johansson, A Melin, B Sjöberg, K Trichopoulos, D Trichopoulou, A Lagiou, P Mattiello, A Tumino, R Masala, G Agnoli, C Boeing, H Aleksandrova, K Brennan, P Franceschi, S Roulland, S Casabonne, D de Sanjose, S Sanchez, M Huerta, J Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title | Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title_full | Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title_fullStr | Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title_full_unstemmed | Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title_short | Lag-times between lympho-proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia (CLL): a prospective analysis using plasma soluble CD23. |
| title_sort | lag times between lympho proliferative disorder and clinical diagnosis of chronic lymphocytic leukemia cll a prospective analysis using plasma soluble cd23 |
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