The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes

BACKGROUND. Tumor necrosis factor (TNF)-α and other cytokines are involved in the pathogenesis of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), but their prognostic significance in these diseases is unknown. In the current study, the authors assessed the association between serum levels of various cytokines and clinical outcomes in patients with untreated AML or high-risk MDS. METHODS. Serum levels of TNF-α, interleukin (IL)-1 receptor antagonist, IL-6, IL-10, and endostatin were measured in patients with AML or high-risk MDS who presented for treatment at The University of Texas M. D. Anderson Cancer Center from September 1994 through January 2001. Univariate and multivariate analyses were performed to test for correlations with clinical outcomes. RESULTS. Higher TNF-α levels were found to correlate with poorer performance status; higher leukocyte counts; higher levels of β₂-microglobulin, creatinine, uric acid, and alkaline phosphatase; lower levels of creatinine clearance and albumin; baseline infection; and M4-M5 AML subtypes. TNF-α levels <10 pg/mL were associated with higher rates of complete remission (P = .003), survival (P = .0003), and event-free survival (EFS) (P = .0009). However, on multivariate analyses, TNF-α level ≥10 pg/mL was not found to be an independent factor predicting clinical outcomes, but became statistically significant when leukocyte count was excluded from the models. The other cytokines were not found to be predictive of clinical outcomes. CONCLUSIONS. High serum TNF-α level is an adverse prognostic factor for survival and EFS in patients with untreated AML or high-risk MDS.