PB2214 INFLAMMATORY BIOMARKERS IN PHILADELPHIA‐NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS AND THE IMPACT OF SMOKING
Authors: V. Skov, K. A. Zervides, V. Nersesjan, L. Kjaer, A. L. Sørensen, H. C. Hasselbalch
Journal: HemaSphere (2019)

Background: The Philadelphia‐negative myeloproliferative neoplasms (MPNs) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Chronic inflammation and a deregulated immune system are considered important for clonal evolution and disease progression. We hypothesize that patients with MPN and MPN‐suspects (MPNsp; patients not having MPN but a biochemical profile imitating MPN) have elevated values of inflammatory biomarkers, which are greatly influenced by smoking. Aims: The aim of this retrospective cross‐sectional study was to investigate various inflammatory biomarkers in subjects with MPN and MPNsp at the time of diagnosis and the impact of smoking on these variables. Methods: A total of 252 subjects were enrolled in the study with 108 having MPN (40 PV, 22 ET, and 46 PMF) according to the WHO 2008 diagnostic criteria. Most of the remaining 144 subjects not having a hematological disease —had elevation of one or more blood cell count and were categorized as “MPNsp”. At the time of diagnosis, blood tests, medical history including medication, smoking history and comorbidities along with results of abdominal ultrasound were registered. Inflammatory biomarkers (leukocytes, C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, fibrinogen, haptoglobin, and fibrin D‐dimer) of MPN patients were compared with MPNsp by risk ratio calculations and Mann‐Whitney‐U tests. Biomarkers of smokers were compared with non‐smokers in both groups. Results: The PV group had significantly lower values of fibrinogen median (range): (9.3(1‐14.8) vs 11.1(5.6‐29.4) p &lt; 0.001) and erythrocyte sedimentation rate (ESR) (2(1‐12) vs 5(1‐95) p &lt; 0.001) compared with the MPNsp. The PV and primary myelofibrosis (PMF) group had significantly lower values of haptoglobin (1.02(0.36‐3.03) vs 1.56(0.32‐5.91) p &lt; 0.001 and 1.2(0.18‐4) vs 1.56(0.32‐5.91) p = 0.003, respectively) and higher values of leukocytes (11.6(5.0‐26.3) vs 8.5(2.7‐135) p &lt; 0.001 and 10.4(3.8‐65) vs 8.5(2.7‐135) p = 0.002, respectively) than the MPNsp, and the ET and PMF groups had significantly higher values of fibrin D‐dimer (0.35(&lt;0.15‐0.96) vs 0.17(0.15‐2.75) p = 0.007 and 0.28(&lt;0.15‐2.13) vs 0.17(0.15‐2.75) p = 0.01, respectively) and ESR (8.5(2‐42) vs 5(1‐95) p = 0.005 and 9(2‐62) vs 5(1‐95) p &lt; 0.001, respectively) compared with the MPNsp. Smokers had significantly higher levels of fibrin D‐dimer (0.18 (&lt;0.15‐2.75) vs &lt;0.15 (&lt;0.15‐0.94) p &lt; 0.05), C‐reactive protein (CRP) (4.5 (&lt;2.9‐96) vs &lt;2.9 (&lt;2.9‐38) p &lt; 0.05), fibrinogen (12 (6‐29) vs 10.3 (5.6‐18.1) p &lt; 0.001, leukocytes (9 (2.7‐135) vs 7.8 (3.9‐20) p = 0.006), and haptoglobin (1.67 (0.32‐5.91) vs 1.40 (0.48‐2.51) p = 0.004) compared with never smokers in the MPNsp. No significant differences were found between smokers and never smokers in the MPN group. Summary/Conclusion: This study has shown that patients with MPN and, for the first time, MPNsp were associated with a low‐grade inflammatory state as assessed by abnormal levels of inflammatory biomarkers at the time of diagnosis. In addition, we report significantly higher levels of inflammatory biomarkers in smokers compared with never smokers in MPNsp possibly reflecting that smoking has a great impact on circulating levels of these biomarkers. Follow‐up studies are being planned aiming at clarifying the prognostic values of these biomarkers in MPNsp and patients with MPN.