Association of Inflammatory Markers and Blood Cell Counts and the Risk of Leukemia in the Swedish Amoris Cohort

Background: The presence of myeloid-derived inflammation is associated with different malignancies, including Leukemia. Certain risk factors (i.e., age, exposure to carcinogens including chemical and radiation), common gene mutations (such as the BCR-ABL fusion gene), and inflammatory markers (such as C-reactive protein (CRP)) have been associated with the risk of developing Leukemia, however cost-effective and widely acceptable predictor markers are not yet available. This study aimed to investigate the association of standard laboratory inflammatory biomarkers and blood cell counts and the long-term risk of Leukemia in a cohort of healthy individuals.

Methods: Individuals from the Swedish Apolipoprotein Risk Study (AMORIS) cohort (n=124609, Male 56.7% vs. Female 43.3 ,>20 years of age) with baseline measurements of C-reactive protein (CRP), albumin, haptoglobin, white blood cell count, mean corpuscular volume (MCV) and platelets were included in the study. Multivariable cox proportional hazard regression analysis adjusted for age, sex, comorbidities (CCI), and socioeconomic status was performed to assess the association of the biomarkers and leukemia diagnosis (ICD-7 (204) Swedish National Cancer Register linkage). Individuals with a leukemia diagnosis within a year of the blood measurement were excluded to account for reverse causation. Considering the time of diagnosis and version of ICD, which was used, it was not possible to stratify patients based on current leukemia classification, including myeloid/ lymphoid or acute/ chronic.

Results: A total of 218 participants (0.2%) developed leukemia over a median follow-up time of 17.54 years. Albumin (leukemia free mean=43.23 vs leukemia mean=42.90 (g/l); p<.001) WBC (leukemia free mean=6.62 vs leukemia mean=9.71 (WBC*×10 ⁹/L); p<.001) and platelets (leukemia free mean=257.00 vs leukemia mean=248.99 (Platelets×10 ⁹/L); p<.001) were all statistically significantly associated with risk of leukemia. When analyzing continuous values, the Hazard Ratio (HR) of albumin was: 1.04 (95%Confidence Interval (CI): 0.98-1.09); the HR of WBC was: 1.09 (95%CI 1.08-1.10) and HR for platelets was: 0.99 (95%CI 0.99-1.00). The analyses of the quartiles presented similar trends, albumin (HR Q4 vs Q1: 1.45 (95%CI 0.90-2.32);HR Q3 vs Q1: 1.62 (95%CI 1.04-2.52); HR Q2 vs Q1: 1.80 (95%CI 1.17-2.78)) (p for trend= 0.006), WBC (HR Q4 vs Q1: 3.57 (95%CI 2.38-5.36) ;HR Q3 vs Q1: 1.50 (95%CI 0.96-2.37); HR Q2 vs Q1: 0.84 (95%CI 0.51-1.40)) (p for trend= 0.08) and platelets (HR Q4 vs Q1: 0.77 (95%CI 0.54-1.11) ;HR Q3 vs Q1: 0.63(95%CI 0.43-0.92); HR Q2 vs Q1: 0.58 (95%CI: 0.40-0.86)) (p for trend =0.003).

Conclusion: The present study presented a positive association between increasing albumin levels and high numbers of WBC and risk of Leukemia, while a negative association was found with high platelet counts, which highlight these markers as potential markers of long-term risk of Leukemia. The potential clinical use of these markers in the early detection of leukemia needs to be evaluated in further studies.