The Serum Spectrum Of Cytokines In Patients With NK/T-Cell Lymphoma and Its Cilincial Significance In Survival

Cai, Qichun; Huang, Hui-qiang; Bai, Bing; Yan, Gao; Li, Jiang; Lin, Suxia; Xia, Yi; Wang, Xiaoxiao; Lu, Jiabin

doi:10.1182/blood.V122.21.1759.1759

Abstract

Backgroud

Natural/killer T-cell lymphoma (NK/TCL) was previously named as lethal midline granuloma. Most patients presented with inflammatory symptoms such as fever and necrosis, which was associated with poor survival. It is still unclear what exactly the role of severe inflammation on the pathogenesis and development of NK/TCL, and there has been few report about the serum cytokines profile and its clinical significance in patients with NK/TCL.

Patients and Methods

From January 2005 to December 2012, the serums and paraffin embed tissues of 59 patients with NK/TCL in Sun Yat-sen University Cancer Center were collected. The Human Cytokine 25-Plex Panel kits (Invitrogen) were used to detect the serum level of the cytokines. And the real-time quantitative polymerase chain reaction (RT-PCR) was employed for detection of the plasma EBV-DNA copies.

Results

Overall, fifty-nine patients with NK/TCL were analyzed. There were 44 male patients. The median age was 39 years (range 10-69 years). There were 37, 5 and 17 patients diagnosed as stage I, II and IV disease, respectively. Forty-one patients had B symptoms and ten patients were diagnosed hemophagocytic syndrome. Fifty-eight patients were followed up, the median follow-up time was 25 (0.2¨C70) months. Comparing with the 12 normal control cases, there were high proinflammatory cytokines and chemokines detected in most patients with NK/TCL(without hemophagocytic syndrome, HPS), including, interleukin-6 (IL-6)(2.56 (0.00-22.29) pg/ml), IL-1ra(88.98 (0.00-1210.05) pg/ml),interferon-¦Ã(IFN-¦Ã)(2.78 (0.00-61.60) pg/ml), IP-10 (41.85 (0.00-1057.41) pg/ml),MIG(49.90 (0.00-799.00) pg/ml), IL-10(0.43 (0.00-13.48)pg/ml), sIL-2R(168.82 (0.00-1916.61) pg/ml),IL-15(0.00(0.00-443.76) pg/ml)(datum express the median serum concentration of cytokines and their range). The serum levels of these cytokines and chemokines mentioned above dramatically increased in 10 patients with hemophagocytic syndrome. The serum concentration of these proinflammatory cytokines and chemokines was notably higher in patients with fever, advanced stage, and microenvironment NF-kB alternative pathway (P52) activation. In patients with P52 activation, the concentration of these cytokine were higher in those plasma EBV-DNA copies ≥10³copy/ml (P≤¼0.05). Multivariate analysis showed that the Korean Prognostic Index (KPI)(P=0.003), the serum concentration of IL-6 (P=0.035) and IL-2R(P=0.044) were independent prognostic factors. High serum IL-6 and IL-2R correlates with poor survival. Twenty-nine patients with serum IL-6 level≤3.97pg/ml, had better survival, with 68.0±8.8% of 3-year overall survival (OS); while 3-year OS of the higher serum IL-6 group was 21.3±8.1% (P=0.001).

Conclusion

≤°Our study indicate that patients with NK/TCL had special serum proinflammatory cytokines and chemokines profile, and these cytokines were notably higher in those with fever, advanced stage, the NF-kB alternative pathway activation in microenvironment, and EBV-DNA copies ≥10³copy/ml. Moreover, high serum concentration of IL-6 and IL-2R were correlated with poor survival.