The relationship between serum ferritin level and fibrosis and splenomegaly in myelofibrosis.

Am J Blood Res 2020;10(6):345-350 www.AJBlood.us /ISSN:2160-1992/AJBR0124083 Original Article The relationship between serum ferritin level and fibrosis and splenomegaly in myelofibrosis Osman Yokus2, Betul Yigit1, Hasan Goze2, Istemi Serin2 Department of Internal Medicine, University of Health Sciences, Istanbul Training and Research Hospital, Istanbul, Turkey; 2Department of Hematology, University of Health Sciences, Istanbul Training and Research Hospital, Istanbul, Turkey 1 Received October 13, 2020; Accepted November 27, 2020; Epub December 15, 2020; Published December 30, 2020 Abstract: Introduction: Myelofibrosis (MF) is a disease in which the grade of bone marrow fibrosis increases in proportion to the degree of extramedullary hematopoiesis and splenomegaly. Associated with increased cytokines and inflammation, anemia deepens and an increase in serum ferritin levels is also expected. There are no studies addressing the relationship between ferritin and splenomegaly or fibrosis. In this study, the relationship between serum ferritin level and splenomegaly and bone marrow fibrosis was examined. Material and Method: The study was performed retrospectively in 46 MF cases diagnosed between 2012 and 2020. MF was divided into 3 separate subgroups: Primary myelofibrosis, secondary myelofibrosis and myeloproliferative neoplasms (MDS/MPN) with myelodsplastic syndrome. Results: Thirty (28.3%) of cases were PMF, 26 (56.5%) were SMF and 7 (15.2%) were MDS/ MPN. There was no relation found between serum ferritin and splenomegaly in none of the cases or subgroup analysis (for PMF p: 0.564, for SMF p: 0.192, for MDS/MPN p: 0.364). There was a statistically significant relationship between serum ferritin and marrow fibrosis within the group of ages 60 years and older (p: 0.016). Discussion and Conclusion: Disruption of hematopoiesis and progressive splenomegaly causes an increase in iron stores associated with an increased need for transfusion. This causes iron-related organ toxicity and bone marrow hematopoiesis disruption, leading to an increase in morbidity. We see that a significant relationship between ferritin and fibrosis has been revealed in the group aged 60 years and older. It is an unprecedented study in the literature in terms of both examining the relationship ferritin and fibrosis or splenomegaly and its results. Keywords: Myelofibrosis, splenomegaly, ferritin, prognosis Introduction Myelofibrosis (MF), which is one of the Philadelphia negative chronic myeloproliferative neoplasms, appears as a disease with bone marrow fibrosis, splenomegaly and pancytopenia [1, 2]. MF may be divided into groups such as primary myelofibrosis (PMF), secondary myelofibrosis (SMF) such as post essential thrombocythemia myelofibrosis (post-ET MF) and post polycythemia vera myelofibrosis (post PV MF) and myeloproliferative neoplasms with myelodisplastic syndrome (MDS/MPN). Organ toxicities that develop as a result of increasing deepening cytopenia and increasing erythrocyte transfusion increase mortality [1-3]. Iron accumulation in the bone marrow over time increases the reactive oxygen derivatives and has a toxic effect on hematopoiesis [4]. Disruption of hematopoiesis and progressive splenomegaly causes an increase in iron overload associated with increased need for transfusion. This causes iron-related organ toxicity and bone marrow hematopoiesis disruption, leading to an increase in morbidity [4]. Therapies that reduce the need for transfusion and lower the level of serum ferritin are used for this purpose. It also contributes to improvement in hematopoiesis by reducing the iron level [5]. Iron accumulates in different organs, causing toxicity, stimulating fibrosis and disrupting the function of many organs [6]. In one reported case, a 67-year-old male patient with PMF was reported to achieve partial transfusion independence with iron chelation therapy [7]. In another study [8], it was indicated that survival Ferritin and fibrosis in myelofibrosis rate increased after iron-binding therapies in patients with PMF. Currently, MF is the only curative treatment for allogeneic stem cell transplantation (ASCT) and only a few of the patients are considered suitable for the transplant. Palliative treatments are often preferred for this reason. In some recent publications, the negative effect of iron load on long-term morbidity and mortality has been reported in transplant cases [9-11]. In one study, 68.9% of those with ASCT were found to have ferritin levels above 500 ng/ml and it was reported that complications were higher in the early post-transplant cases with high ferritin levels [11]. Additionally, splenomegaly targeted therapies are recommended in MF before ASCT [12, 13]. Bone marrow fibrosis has also been reported decreasing the regression of splenomegaly. In patients with MF, the progression of the disease and splenomegaly also increases serum ferritin level. Literature review shows that there are no studies examining the increase of ferritin and splenomegaly or fibrosis. In this study, the goal was to investigate the relationship between all subgroups, serum ferritin level and fibrosis and splenomegaly. Material and method plastic syndrome (MDS/MPN). Post polycythemia vera MF and post essential thrombocythemia MF were considered as SMF. Ferritin level, spleen size and treatment The ferritin level was considered as high above 300 ng/ml (reference range 30-300 ng/ml) [15]. In ultrasonography, the spleen vertical size was accepted as splenomegaly over 120 mm [16]. Patients who received JAK inhibitor (ruxolitinib) and iron chelation therapy for minimum of 3 months within the past year were analyzed as subgroups. Additionally, the patients were divided into two groups based on the number of transfusions they received within the last year: with minimum of 10 units and above, under 10 units or without erythrocyte suspension transfusions. Exclusion criteria Patients received splenic radiotherapy, had other comorbidities that may cause splenomegaly, received iron replacement therapy within the last year or had a congenital or acquired disease associated with iron deposition were not included in the study. Statistical analysis Serum ferritin and other biochemical parameters, cytogenetic results such as JAK2 mutation, bone marrow biopsy pathology results and ultrasonography reports were recorded. The cases which meets the definitive diagnostic criteria according to the World Health Organization (WHO) 2016 Myeloproliferative Neoplasms Diagnostic Criteria were included in the study [14]. NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) program was used for statistical analysis. Descriptive statistical methods (mean, standard deviation, median, frequency, ratio, minimum, maximum) were used evaluating the study data. The suitability of the quantitative data for normal distribution was tested by Shapiro-Wilk Test and graphical evaluations. Kruskal Wallis Test was use (...truncated)