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Abstract
Levels of soluble interleukin-2 receptor alpha (sIL-2Rα) are known to increase in the sera of patients with certain malignancies, including malignant lymphoma. This study aimed to assess the clinical significance of the sIL-2Rα level in non-Hodgkin's lymphoma (NHL). We used ELISA to measure the sIL-2Rα levels in 48 newly diagnosed and untreated patients with NHL and evaluated the correlation between the sIL-2Rα levels and clinical characteristics and the International Prognostic Index (IPI). We monitored serum sIL-2Rα in 7 patients to compare the changes in their clinical progress with these levels. High levels of serum sIL-2Rα (≥2,000 U/mL) correlated well with parameters defining the high risk group according to the IPI, i.e., high tumor burden at diagnosis (stage III+IV) and lactate dehydrogenase ≥472 U/L. The levels were also associated with B symptoms, bone marrow involvement, and poor response to therapy. The sIL-2Rα level decreased during complete remission and was elevated during disease progression or relapse. A high level of sIL-2Rα was significantly associated with a low survival rate. These results suggest that serum sIL-2Rα might be useful as a biomarker for evaluating the prognosis of patients with NHL at the time of diagnosis and during therapy. A well-controlled, large-scale study is needed to clarify the clinical significance of sIL-2Rα in specific groups of NHL.
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Fig. 1.
Serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels according to the International Prognostic Index (IPI) risk group (Kruskall-Wallis test, P=0.005).
Fig. 2.
Serial analysis of serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels in non-Hodgkin's lymphoma patients showing complete remission (CR), through stable disease (SD) or partial remission (PR); sIL-2Rα levels in relation to the timing of chemotherapy, and with respect to radiographic evaluations. (A) A 36-yr-old man with anaplastic large cell lymphoma in the inguinal lymph nodes treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). (B) A 40-yr-old man with diffuse large B cell lymphoma in the small bowel lymph nodes treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). (C) A 60-yr-old man with B cell malignant lymphoma in the oral cavity treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP).
Fig. 3.
Serial analysis of serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels in non-Hodgkin's lymphoma patients showing recurrence or progressive disease (PD) after partial remission (PR); sIL-2Rα levels in relation to the timing of chemotherapy, and with respect to radiographic evaluations. (A) A 48-yr-old woman with follicular lymphoma in the axillary lymph nodes treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). (B) A 64-yr-old man with angioimmunoblastic T cell lymphoma in the neck treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). (C) A 53-year-old man with angioimmunoblastic lymphoma in the cervical lymph nodes treated with CHOP.
Fig. 4.
Overall survival curves for non-Hodgkin's lymphoma patients in relation to soluble interleukin-2 receptor alpha (sIL-2Rα) level; overall survival curves according to low (<2,000 U/mL) versus high (≥2,000 U/mL) level of sIL-2Rα (Log-rank test, P=0.041).
Table 1.
Serum sIL-2Rα levels according to the characteristics of NHL patients
| Clinical factors | N of cases | sIL-2Rα (U/mL) | P value∗ | |
|---|---|---|---|---|
| Median | Range | |||
| Gender | ||||
| Male | 29 | 1,940 | 283-15,033 | NS |
| Female | 19 | 2,433 | 495-11,334 | |
| Age | ||||
| <60 | 30 | 1,611 | 283-13,367 | NS |
| ≥60 | 18 | 3,840 | 594-15,033 | |
| Stage | ||||
| I+II | 25 | 1,197 | 283-11,849 | 0.001 |
| III+IV | 23 | 4,559 | 546-16,033 | |
| LD (U/L) | ||||
| <472 | 19 | 1,197 | 476-8,369 | 0.004 |
| ≥472 | 29 | 3,826 | 283-15,033 | |
| Extranodal involvement | ||||
| Absent | 15 | 1,394 | 283-15,033 | NS |
| Present | 32 | 2,358 | 476-13,367 | |
| B symptom | ||||
| Absent | 26 | 1,646 | 283-8,369 | 0.001 |
| Present | 17 | 4,099 | 546-15,033 | |
| Bone marrow involvement | ||||
| Absent | 34 | 1,735 | 283-11,849 | 0.004 |
| Present | 14 | 5,833 | 569-15,033 | |
| Treatment response (CR) | ||||
| Yes | 21 | 688 | 283-4,812 | 0.001 |
| No | 25 | 4,386 | 739-15,033 | |
Table 2.
Univariate analysis on overall survival in NHL patients
| Clinical factors | N of cases | Overall survival, months (rate, %) | P value∗ |
|---|---|---|---|
| Gender | |||
| Male | 29 | 24.1 (72) | NS |
| Female | 19 | 28.7 (89) | |
| Age | |||
| <60 | 30 | 24.0 (73) | NS |
| ≥60 | 18 | 27.4 (88) | |
| Stage | |||
| I+II | 25 | 27.5 (88) | NS |
| III+IV | 23 | 23.7 (69) | |
| LD (U/L) | |||
| <472 | 19 | 28.2 (89) | NS |
| ≥472 | 29 | 24.3 (72) | |
| Extranodal involvement | |||
| Absent | 15 | 29.0 (93) | NS |
| Present | 32 | 24.0 (71) | |
| B symptom | |||
| Absent | 26 | 28.7 (92) | 0.01 |
| Present | 17 | 21.8 (58) | |
| Bone marrow involvement | |||
| Absent | 34 | 21.8 (85) | NS |
| Present | 14 | 21.0 (64) | |
| sIL-2Rα (U/mL) | |||
| <2,000 | 22 | 27.9 (90) | 0.041 |
| ≥2,000 | 26 | 23.0 (69) |
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