Serum levels of tumour necrosis factor-α predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome

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Abstract
Summary We measured pretreatment serum levels of tumour necrosis factor‐α (TNF‐α) and interleukin‐1β(IL‐1β) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF‐α and IL‐1β levels were measured using commercially available enzyme‐linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1–2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF‐α (80.5 ± 64.8 vs 8.1 ± 4.2 ng/l, P < 0.001) and IL‐1β (60.4 ± 49.9 vs 8.9 ± 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF‐α than non‐responders (21.6 ± 26.2 vs 106.3 ± 60.8 ng/l, P < 0.001), whereas IL‐1β concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 ± 48.9 vs 73.4 ± 48.2 ng/l, P= 0.120). It is noteworthy that TNF‐α levels were within the normal range in all responsive patients but one, whereas all non‐responders presented elevated cytokine concentrations. No relationship was found between TNF‐α or IL‐1β values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre‐treatment TNF‐α levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.