PB1873 PREDIAGNOSTIC TRAJECTORIES OF HEMOGLOBIN, LYMPHOCYTE AND PLATELET COUNT IN PATIENTS DEVELOPING CLL.
Authors: Andersen M. , Grand M. , Siersma V. , Andersen C. , Niemann C. 
Published: June 2019

Background:

CLL is a slowly developing disease, but information about development in hemoglobin, platelet and lymnphocyte counts prior to CLL diagnosis is sparse and prediagnostic trajectories of such need exploring. A better understanding of disease progression will generate earlier treatment options and may even lead to preventive approaches. Despite general agreement that CLL patients have lymphocytosis in the years preceding a diagnosis, there is less certainty as to how why and when biomarkers develop. Therefore, we undertook a cohort study comparing hemoglobin, lymphocyte and platelet count trajectories in patients with CLL with unmutated IGHV (CLLunmut), mutated IGHV (CLLmut) compared with control individuals.

Aims:

To define how biomarker trajectories of patients with CLL differ from control individuals.

Methods:

All patients diagnosed with CLL in Greater Copenhagen between 2008 and 2016 were matched to 15 randomly selected control individuals matched on sex and age at diagnosis. We retrieved data on all CLL patients and their control individuals from the Copenhagen Primary Care Laboratory database, which contains results from all prediagnostic tests requested by general practitioners in Copenhagen from 2000 to 2015. We estimated the population‐averaged trajectories separately for each biomarker using generalized estimating equations. We included time to diagnosis, classification group (controls, IGHVunmut and IGHVmut), sex and age at diagnoses as covariates, along with an interaction between time to diagnosis and classification group.

Results:

Of the 778 patients who developed CLL, 437 were IGHVmut, 200 IGHVunmut and 141 patients had unknown IGHV status. We included 71.957 prediagnostic lymphocyte count measurements, 111.465 platelet count measurements, 107.029 CRP measurements and 111585 hemoglobin measurements. The lymphocyte‐count‐trajectories differed significantly between the IGHVmut and IGHVunmut subgroups. From 8 years prior to diagnosis, the IGHVmut subgroup had a slower increase from a higher starting point compared to the IGHVunmut subgroup, which increased closer to diagnosis with a steeper slope resulting in an overall higher lymphocyte count at time of diagnosis.

Hemoglobin decreased linearly over time in all groups. In line with the findings for lymphocytosis, the platelet count decreased steadily from 8 years prior to diagnosis for patients with IGHVmut status, whereas the trajectories of IGHVunmut patients decreased dramatically 5 years prior to diagnosis for IGHVunmut patients.

Summary/Conclusion:

Here, we reveal that IGHVunmut patients develop lymphocytosis and thrombocytopenia within 5 years prior to diagnosis, much closer to diagnosis than IGHVmut patients do. By defining the time point of CLL development for these two disease entities, we identify the window of opportunity for population‐based studies to unravel the mechanisms of CLL progression, paving the road for personalized preventive interventions.

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