Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma

BACKGROUND: Recently investigators have worked to identify prognostic factors in non-Hodgkin's lymphoma (NHL) so an appropriate therapeutic plan can be put in action. The aim of the present study was to assess the prognostic significance of serum soluble tumor necrosis factor receptor (sTNF-R) 2 in aggressive NHL. METHODS: One hundred and ten consecutive patients with aggressive NHL who were previously untreated (diffuse large B-cell lymphoma; 94, peripheral T-cell lymphoma; 16) were prospectively enrolled in this study between 1997 and 2002. The patients were treated with 6-8 cycles of CHOP or THP-COP regimens. RESULTS: High serum sTNF-Rs level was associated with some poor prognostic factors and low complete remission rate. Patients with high sTNF-R1 (4 ng/mL and over) and sTNF-R2 (15 ng/mL and over) at onset had significantly lower survival rates (5 yr: 19%, 19%) than those with low sTNF-R1 (under 4 ng/mL) and sTNF-R2 (under 15 ng/mL) (62% and 69%), respectively (P < 0.0005 and 0.0001). Multivariate analysis employing sTNF-R2 and some conventional prognostic factors demonstrated that a combination of sTNF-R2 and performance status, and that of sTNF-R2, sIL-2R, and LDH were significant prognostic factors for poor overall survival and for poor event-free survival, respectively. In addition, we attempted to use sTNF-R2 in combination with the international prognostic index (IPI). The patients in the high risk group and those with high sTNF-R2 in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low risk group and those with low sTNF-R2 in LI/HI risk group (P < 0.0001). CONCLUSIONS: The results suggest that a high serum sTNF-R2 level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.