Serum-Soluble Interleukin-2 Receptor (sIL-2R) Is an Extremely Strong Prognostic Factor for Patients with Peripheral T-Cell Lymphoma, Unspecified (PTCL-U).

Introduction: PTCL is a heterogeneous group of neoplasms presenting as advanced disease and are characterized by widespread dissemination, aggressive behavior, and a very poor outcome. We have previously reported serum concentration of sFas, sTNFR-2 and sIL-2R predict a clinical outcome of patients with aggressive NHL. There are many differences between PTCL-U and DLBCL. After introduction of rituximab to treat for B cell lymphoma, the clinical difference between B cell lymphoma and T cell lymphoma is clearer. It is necessary to examine the prognostic factor in PTCL besides DLBCL.

Patients and methods: We investigated all patients of PTCL diagnosed between January 1995 and December 2006. We considered eligible for this study all patients with histologically confirmed diagnosis of PTCL-U, according to the WHO classification. Patients were assigned to receive eight cycles of CHOP or THP -COPtherapy. Patients with a bulky mass received radiotherapy after chemotherapy. Patients who relapsed or had disease progression after CHOP or THP-COP received the P-IMVP-16/CBDCA regimen, consisting of mPSL, IFM,MTX, VP-16, and CBDCA, as a second-line regimen. All follow-up data were updated on March 1, 2007.

Results: We measured serum sIL-2R levels in a consecutive series of 27 previously untreated patients with PTCL-U. The median age was 59 years (14–79 years), and there was a male preponderance, with a male- to-female ratio of 4.4. The median serum sIL-2R level of the different IPI risk groups was as follows: 488 (176 – 3400)U /ml for the L risk group, 2400 (423–72800) U /ml for the LI risk group, 2712(570 – 58900) ng/ml for the HI risk group, and 8245 (2398 – 80450) U /ml for the H risk group (P<0.001). The 27 patients with PTCL-U were divided into two groups with different sIL-2R levels ranging from 176 U/ml to 80450 U/ml, a cut-off value of 2000U /ml. The cutoff line of a serum sIL-2R level is set to 2000 IU/ml in our past report. The CR rate of patients with an sIL-2R level of less than 2000U /ml and 2000U /ml and over was 88.9% and 50.0%, respectively (P<0.0005). After a mean follow-up of 137 months, the cumulative probability of survival at 5 years was 35.6%. The OS rate was significantly worse in patients with poor PS (>1) (P<0.01), unfavorable IPI (P<0.05). The 5-year OS rates for patients with an sIL-2R level of less than 2000U /ml and 2000U /ml and over were 100% and 10.0%, respectively (P<0.01). Multivariate analyses employing these factors demonstrated that only high serum sIL-2R were independent prognostic factors (P<0.05).

Discussion: High serum levels of sIL-2R have been demonstrated in several diseases. In our examination, it is thought that sIL-2R more clearly reflects the prognosis in the patients with PTCL-U compared with DLBCL. The activated T cells produce sIL-2R in B cell lymphoma. It is thought that in PTCL-U, the activated T cells produce sIL-2R and in addition, the lymphoma cells produce sIL-2R. Therefore, sIL-2R more clearly reflects the prognosis in the patients with PTCL-U compared with DLBCL. Soluble IL-2R can be easily measured by using ELISA. It is important to ensure that these analyses can be performed quickly and easily. Soluble IL-2R clearly reflects the prognosis of PTCL-U. The sIL-2R should be used to stratification of the patient with PTCL-U as biological prognostic factor besides IPI.

Conclusion: Serum sIL-2R is a useful tool as a significant prognostic factor for PTCL-U.