Levels of Tumor Necrosis Factor Alfa and Iron Status in Pediatric Patients with Newly Diagnosed Solid Tumors

Abstract Background Tumor necrosis factor alfa (TNF-α) plays a crucial role in the etiopathogenesis of cancer related anemia. Aim: To assess the levels of TNF-α, erythropoietin (EPO), and iron status in relation to anemia in children with newly diagnosed solid tumors. Methods we measured serum levels of TNF-α, EPO and assessed iron status using enzyme linked immunosorbent assay in 42 patients (20 non-anemia and 22 anemic) with newly diagnosed solid malignancies and compared them to 25 age- and sex-matched healthy controls. Results Among the 42 patients enrolled, 14 (33.3%) patients had brain tumors, seven (16.6%) were diagnosed with neuroblastoma, and four (9.5%) with Wilms tumor. The mean hemoglobin levels were 12.39±0.8 g/dl and 9.57±1.3 g/dl in non-anemic and anemic patients respectively. We found significantly higher levels of serum TNF-α and lower EPO levels among patients when compared to the control group (p < 0.001). A post hoc analysis showed a significantly higher TNF-α and lower EPO levels among anemic versus controls (p < 0.001) and non-anemic versus control (p < 0.001). A significant positive correlation was found between both EPO and TNF-α in both anemic and non-anemic group (r = 0.48, p = 0.024) and (r = 0.44, p = 0.021) respectively. However, the median (IQR) levels of both TNF- α and EPO were comparable between both anemic and non-anemic patients (306 (237.5) pg/ml versus 353 (156.2) pg/ml, p = 0.47) and (93 (46) mIU/ml versus 87 (51) mIU/ml, p = 0.48) respectively. The median (IQR) levels of serum ferritin and transferrin saturation index (TSI), as well as; serum TNF-α did not correlate with any of the red cell indices yet; directly correlated with platelet counts (r = 0.491, p = 0.02). Conclusion Children with solid malignancies have significantly higher levels of TNF-α and impaired EPO responses than normal children, however, no significant effect was observed for either on hemoglobin and red cell indices. Whether the positive relationship between TNF- α and EPO suggest other mechanisms of TNF- α related anemia needs further studies.