Abstract
Objective. Consequently, activation of the Jak-STAT pathway plays a central role in the pathogenesis of primary myelofibrosis and resulting profound chronic inflammation. The Neutrophil-to-Lymphocyte Ratio (NLR) is an inflammatory biomarker that, whose elevation, has been consistently associated with poor clinical outcomes in a variety of malignancies. However, the results of studies investigating the effect of NLR on overall survival (OS) in patients with PMF remain conflicting. Preliminary results of this study, based on a smaller patient cohort (n=72), were previously presented as an oral presentation at the 12th SOHO Turkiye Meeting and were later accepted as a poster presentation at the SOHO 2025 Annual Meeting. In the current analysis, we have significantly expanded our patient cohort to 128, enabling us to perform a more comprehensive and robust evaluation. The aim of this study was to determine how NLR predicts OS in PMF patients.
Methodology. Patients with diagnosis Primary Myelofibrosis fulfilling WHO 2016 criteria were retrospectively analysed in the period from 2011 to 2024. All patients were registered at the National Hematology and Transfusion Center of Azerbaijan. All data were collected from medical records. Mann-Whitney U test, Kruskal-Wallis test, χ2 (chi-squared) test were used where appropriate. Survival analyses were performed using the Kaplan-Meier method and Cox regression analysis. ROC curve analysis using survival status as a classification variable was performed to determine optimal cut-off values for survival analyses. p-values <0.05 were considered statistically significant.
Results. A total of 128 PMF patients were evaluated. Of these, 60 (46.87%) were male. Median age was 59 years, 27(21.09%) patients were young(under 50 years). Majority of pateints were JAK2V617F mutated (75%). Median follow-up was 37.16 months. Median overall survival was 131 months.
Median NLR was 4.2 (IQR 4.4), and ROC analysis identified 2.1 as the optimal cut-off, dividing patients into high (>2.1, N=105) and low (≤2.1, N=23) NLR groups.
As expected from NLR, higher values were statistically significantly associated with higher WBC count (p<0.001), higher absolute neutrophil count (p<0.001). No differences in absolute lymphocyte count were observed between the two groups. Higher NLR values were also associated with older age (57 vs 55; p-0.768), high Hgb levels (11.75 IQR 4.4 vs 9.6 IQR 3.65: p-0.13), high platelet count (359.0 IQR 386 vs 280.0 IQR 368; p=0.12), higher LDH level (503.0 IQR 487 vs 446.0 IQR 177.5; p=0.628), lower MPN TSS (10.5 IQR 13.75 vs 21.0 IQR 13.5; p=0.068), but they were not statistically significant. The distribution of IPSS risk categories did not differ significantly between High and Low NLR groups (p=0.839).
At last follow-up, 11 patients (10.5%) in the high NLR group had died compared to 9 patients (39.1%) in the low NLR group. Median OS was 131 month in low NLR group and doesn′t reach in high NLR group. In our cohort, high NLR values were associated with significantly better median OS vs low NLR (p-0.008).
Conclusion. NLR is a simple biomarker of inflammation and its associated worse outcome in various malignancies when elevated. However, the association of elevated NLR in myelofibrosis is controversial. M. Lucijanic and colleagues retrospectively analysed a cohort of 102 patients with myelofibrosis and determined optimal cut-off values for NLR for survival analyses using ROC curve analysis, separating patients into groups with NLR ≥10 (higher NLR) and NLR <10 (lower NLR). In the univariate analyses, patients with myelofibrosis and higher NLR had shorter overall survival than patients with lower NLR (HR=2.05; p=0.030) . Another retrospective study published in the European Journal of Haematology by Laganà et al. analysed data from 140 myelofibrosis patients and found that patients with a baseline NLR ≥2 had a longer OS than patients with NLR <2 . In our study, we identified optimal cut-off values of NLR 2.1- similar to previous as- for survival analysis using ROC curve analysis and compared the high NLR ( >2.1) group with the low NLR. We showed that higher NLR was associated with significantly better OS than lower NLR(p-0.008). The limitations of our study are the retrospective design and the small number of participants. We believe that NLR is a valuable prognostic factor for predicting OS in PMF. However, we need large prospective studies to define the exact cut-off and impact of NLR.
