TY - JOUR

T1 - Pre-diagnostic trajectories of lymphocytosis predict time to treatment and death in patients with chronic lymphocytic leukemia

AU - Andersen, Michael Asger

AU - Grand, Mia Klinten

AU - Brieghel, Christian

AU - Siersma, Volkert

AU - Andersen, Christen Lykkegaard

AU - Niemann, Carsten Utoft

N1 - © The Author(s) 2022.

PY - 2022

Y1 - 2022

N2 - BACKGROUND: The dynamics of pre-diagnostic lymphocytosis in patients with ensuing chronic lymphocytic leukemia (CLL) need to be explored as a better understanding of disease progression may improve treatment options and even lead to disease avoidance approaches. Our aim was to investigate the development of lymphocytosis prior to diagnosis in a population-based cohort of patients with CLL and to assess the prognostic information in these pre-diagnostic measurements.METHODS: All patients diagnosed with CLL in the Greater Copenhagen area between 2008 and 2016 were included in the study. Pre-diagnostic blood test results were obtained from the Copenhagen Primary Care Laboratory Database encompassing all blood tests requested by Copenhagen general practitioners. Using pre-diagnostic measurements, we developed a model to assess the prognosis following diagnosis. Our model accounts for known prognostic factors and corresponds to lymphocyte dynamics after diagnosis.RESULTS: We explore trajectories of lymphocytosis, associated with known recurrent mutations. We show that the pre-diagnostic trajectories are an independent predictor of time to treatment. The implementation of pre-diagnostic lymphocytosis slope groups improved the model predictions (compared to CLL-IPI alone) for treatment throughout the period. The model can manage the heterogeneous data that are to be expected from the real-world setting and adds further prognostic information.CONCLUSIONS: Our findings further knowledge of the development of CLL and may eventually make prophylactic measures possible.

AB - BACKGROUND: The dynamics of pre-diagnostic lymphocytosis in patients with ensuing chronic lymphocytic leukemia (CLL) need to be explored as a better understanding of disease progression may improve treatment options and even lead to disease avoidance approaches. Our aim was to investigate the development of lymphocytosis prior to diagnosis in a population-based cohort of patients with CLL and to assess the prognostic information in these pre-diagnostic measurements.METHODS: All patients diagnosed with CLL in the Greater Copenhagen area between 2008 and 2016 were included in the study. Pre-diagnostic blood test results were obtained from the Copenhagen Primary Care Laboratory Database encompassing all blood tests requested by Copenhagen general practitioners. Using pre-diagnostic measurements, we developed a model to assess the prognosis following diagnosis. Our model accounts for known prognostic factors and corresponds to lymphocyte dynamics after diagnosis.RESULTS: We explore trajectories of lymphocytosis, associated with known recurrent mutations. We show that the pre-diagnostic trajectories are an independent predictor of time to treatment. The implementation of pre-diagnostic lymphocytosis slope groups improved the model predictions (compared to CLL-IPI alone) for treatment throughout the period. The model can manage the heterogeneous data that are to be expected from the real-world setting and adds further prognostic information.CONCLUSIONS: Our findings further knowledge of the development of CLL and may eventually make prophylactic measures possible.

U2 - 10.1038/s43856-022-00117-4

DO - 10.1038/s43856-022-00117-4

M3 - Journal article

C2 - 35603299

VL - 2

JO - Communications Medicine

JF - Communications Medicine

SN - 2730-664X

M1 - 50

ER -