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Agić, D.1, 2; čabarkapa, V.3, 4; Popović, S.1, 2; Perčić, I.1, 2; El Farra, A.1, 2; Nikolić, S.3, 4; Milošević, I.1, 2; Sekulić, B.1, 2; Savić, A.1, 2; Vlaisavljević, N.1, 2; Dragičević, M.1, 2; Urošević, I.1, 2

doi: 10.1097/01.HS9.0000566672.32772.30
Publication Only: Iron metabolism, deficiency and overload

1Clinic for hematology, Clinical Center Vojvodina

2Department of internal medicine

3Department of Pathophysiology and Laboratory Medicine, University of Novi Sad, Faculty of Medicine

4Center of Laboratory Medicine, Clinical Center Vojvodina, Novi Sad, Serbia

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Lymphoma patients, even those without anemia, sometimes have levels of iron metabolism biomarkers outside the normal range. Hepcidin and ferritin, usually elevated in inflammatory and malignant states, are affected by erythropoetic activity. GDF-15 might be included in the process. Its level is elevated in some malignant and non malignant diseases and is associated with worse prognostic outcome.

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Our objectives were to investigate the level of the growth/differentiation factor 15 (GDF-15), hepcidin and iron metabolism biomarkers in patients with lymphoproliferative diseases and to compare these parameters between patients who needed and received lymphoma treatment and those on “watch and wait” regimen.

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This is an ongoing research at the Clinic for hematology, Clinical center of Vojvodina. Patients with comorbidities associated with elevated GDF-15 or hepcidin levels were excluded. The results of 29 lymphoma patients have been analyzed. CBC, ESR, LDH, CRP, β2microglobulin, Fe, transferin, ferritin, soluble transferin receptors, hepcidin, GDF-15 were evaluated in 12 lymphoma patients on “watch and wait”, while in 17 patients who needed treatment the markers were measured before therapy and will be analyzed again after treatment completion. ELISA technique from stored sera was used for GDF-15 and hepcidin evaluation. Informed written consents were collected after Approval of Ethical committee of Clinical center Vojvodina and Faculty of Medicine University of Novi Sad. Mann-Whitney U test and Spearman Rank Order Correlation were performed and p < 0.05 was significant with confidence interval of 95%.

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The first group consisted of 12 patients, median age 64 (interquartile range (IQ) 55 to 67), the second of 17 patients who needed therapy, median age 58 years (IQ 51 to 65).

Significant higher values were in the second group for: GDF-15 592pg/ml (IQ 560 to 680) vs. 840pg/ml (IQ 600 to 980) p < 0.05, hepcidin 6540pg/ml (IQ 6512 to 6552) vs. 6720pg/ml (IQ 6560 to 6920) p < 0.05, and β2microglobulin 2.08 (IQ 2.03 to 2.41) vs. 4.04 (IQ 3.12 to 4.43), p < 0.05. The second group had a significantly lower value of transferin 2.7 g/l (IQ 2.46 to 3.13) vs. 2.24 g/L (IQ 2.06 to 2.59), p < 0.05, Fe 18.2 μmol/l (IQ 15.8 to 23.3) vs. 10 μmol/l (IQ 6.3 to 13.6), p < 0.05, Hg 139 g/l (IQ 135 to149) vs. 126 g/l (IQ 115 to 135) p < 0.05, hematocrit 0.42 (IQ 0.40 to 0.43) vs. 0.39 (IQ 0.35 to 0.41), p < 0.05. There were marked positive correlation between GDF-15 and ESR (r = 0.58, p < 0.05), β2mikroglobulin (r = 0.47, p < 0.05), ferritin (r = 0.44, p < 0.05), and fibrinogen (r = 0.5, p < 0.05), and negative with transferin (r = -0.55, p < 0.05), Fe (r = -0.39, p < 0.05), hemoglobin (r = -0.43, p < 0.05), and hematocrit (r = -0.42, p < 0.05). Hepcidin positively correlated with β2microglobulin (r = 0.6, p < 0.05), and ferritin (r = 0.38, p < 0.05).

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Higher values of GDF-15 and hepcidin in the group of patients who needed therapy might be connected to a larger tumor burden and more aggressive course of lymphoproliferative disease. These data will be evaluated in larger groups of patients, alongside data collected from the second group after treatment completion. The prognostic value of GDF-15, hepcidin, and iron metabolism biomarkers in lymphoproliferative diseases is yet to be determined.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.