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

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.