Biomarker dynamics in B-cell lymphoma: a longitudinal prospective study of plasma samples up to 25 years before diagnosis

The B-cell activation markers CXCL13, sCD23, sCD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of marker-disease association hampers interpretation. In this study, we identified 170 individuals who had donated two pre-diagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level. Notably, we observed strong associations between CXCL13, sCD23, sCD27, and sCD30 and lymphoma risk in blood samples collected 15 to 25 years before diagnosis. B-cell activation marker levels increased among future lymphoma cases over time, while remaining stable among controls. Associations between slope and risk were strongest for indolent lymphoma subtypes. We noted a marked association of sCD23 with chronic lymphocytic leukemia (ORSlope = 28, Ptrend = 7.279 x 10-10). Among aggressive lymphomas, the association between diffuse large B-cell lymphoma risk and slope was restricted to CXCL13. B-cell activation seemed to play a role in B-cell lymphoma development at early stages across different subtypes. Further, B-cell activation presented differential trajectories in future lymphoma patients, mainly driven by indolent subtypes. Our results suggest a utility of these markers in predicting the presence of early occult disease and/or the screening and monitoring of indolent lymphoma in individual patients.

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