Effects of Hydroxyurea Therapy on Inflammatory Markers and Indices in Patients with BCR-ABL Negative Myeloproliferative Neoplasms

Introduction:Chronic inflammation plays a central role in the pathogenesis and progression of Breakpoint Cluster Region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL)-negative myeloproliferative neoplasms (MPNs).Although hydroxyurea is widely used as a cytoreductive agent in this patient population, its impact on systemic inflammation remains unclear.This study aimed to evaluate the effect of hydroxyurea on inflammatory markers and indices in patients with MPNs.Methods: In this retrospective study, 298 patients diagnosed with BCR-ABL-negative MPNs who were followed between 2010 and 2022 were analyzed.Patients were classified as polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), or MPN-unclassifiable (MPN-u) according to the 2016 World Health Organization criteria.Laboratory parameters including leukocyte, neutrophil, lymphocyte, and platelet counts, C-reactive protein (CRP), and lactate dehydrogenase (LDH) were recorded at baseline and at months 3, 6, and 12. Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immuneinflammation index (SIII), were calculated.Statistical analyses were performed using non-parametric tests.Results: Of the 298 patients, 59.4% were male, with a median age of 57 years.The cohort included PV (32.5%),ET (35.2%),PMF (8.7%), and MPN-u (23.5%).Hydroxyurea was used in 158 patients, while 126 patients were followed without cytoreductive therapy.Significant reductions in leukocyte and neutrophil counts were observed in the hydroxyurea group at months 0-3, 0-6, and 0-12 (p<0.001).NLR decreased significantly at months 0-3 and 0-6, while SIII showed significant reductions at months 0-3, 0-6, and 0-12.CRP and LDH levels remained unchanged.No significant inflammatory changes were detected in patients not receiving hydroxyurea.Conclusion: Hydroxyurea treatment was associated with early reductions in inflammatory indices in BCR-ABL-negative MPN patients, possibly reflecting either its myelosuppressive or its potential anti-inflammatory effects.Further prospective studies incorporating cytokine profiling are needed to clarify the mechanisms underlying hydroxyurea's impact on inflammation.