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Department of Medicine; Meyers Primary Care Institute

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Clinical Epidemiology | Hematology | Hemic and Lymphatic Diseases | Immune System Diseases | Immunopathology | Neoplasms | Pathological Conditions, Signs and Symptoms


Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses' Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years ( < 5, 5 to < 10, > /=10) after blood draw. Soluble interleukin-2 receptor-alpha, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (odds ratio: 95% confidence interval: 0.51, 0.43-0.62) persisted more than 10 years after blood draw (odds ratio: 0.70; 95% confidence interval: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis.


Aggressive Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Clinical and Molecular Epidemiology, Indolent Non-Hodgkin's Lymphoma, UMCCTS funding

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Copyright © 2018, Ferrata Storti Foundation. Authors' accepted manuscript posted as allowed by the publisher's author rights policy at

DOI of Published Version



Haematologica. 2018 Jun 21. pii: haematol.2017.183236. doi: 10.3324/haematol.2017.183236. [Epub ahead of print] Link to article on publisher's site

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