Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia

Abstract

Background. The authors conducted a survey of a large cohort of patients with adult T‐cell leukemia (ATL) and a group of human T‐cell leukemia virus type 1 (HTLV‐1) carriers to elucidate whether measurements of soluble interleukin‐2 receptor (sIL‐2R) levels are indicative of ATL tumor burden and correlate with clinical progression. Methods. Using a sandwich enzyme immunoassay, the authors determined sIL‐2R in the serum of 135 patients with ATL diagnosed and subclassified according to the Japan Lymphoma Study Group criteria and in the serum of healthy HTLV‐1 seropositive persons. Also included were patients in the preleukemic state of ATL (pre‐ATL), which is characterized by only slight blood changes but does not fit the diagnostic criteria of ATL. In the five subjects who finally advanced to overt ATL, the authors prospectively performed serial measurements of the receptor. Results. Serial measurements of sIL‐2R levels taken until overt ATL developed showed that these levels in the initial samples were higher than those of control subjects, even when subjects were asymptomatic or in the pre‐ATL state. The serial levels of the five subjects gradually increased despite being in a clinically stable condition, finally reaching markedly high levels at the time ATL became overt. The mean sIL‐2R levels of the smoldering, chronic, acute, and lymphoma subtypes of ATL were 1680 U/ml, 6680 U/ml, 45,940 U/ml, and 34,620 U/ml, respectively (P > 0.01). The sIL‐2R levels of each subtype at the time of diagnosis were more correlated with tumor burden, malignant behavior, and prognosis than lactate dehydrogenase (LDH) levels. In the low, moderate, and high sIL‐2R subgroups, the median survival time and percent survival probability at 2 years was 30.2 months (46.0%), 16.5 months (25.0%), and 7.7 months (15.3%), respectively. Conclusions. Serial measurements of sIL‐2R levels are of clinical importance because changes of the levels correlate with disease progression, especially in early phase of ATL. The data suggest that sIL‐2R may be more useful than LDH. In addition, emphasis may be placed on sIL‐2R as an indicator of ATL progression status and prognosis for survival. The value of this marker in clinical practice should be confirmed prospectively. Cancer 1994; 73:2753–8.

Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers

“…The sIL-2R levels of each subtype at the time of diagnosis appear to be correlated with tumour burden, malignant behaviour, and prognosis. This correlation is better than that observed with LDH [18].…”

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

“…The CD7 and CD8 antigens are usually absent. Factors signifying a poor prognosis include high serum thymidine kinase levels [16,17], high serum soluble interleukin-2 receptor levels [18], high serum b 2 -microglobulin levels [19], high expression of the Ki67 antigen, and high serum parathyroid hormone-related protein levels. The serum neuronspecific enolase (NSE) value positively correlated with serum thymidine kinase activity and serum soluble interleukin-2 receptor levels.…”

Soluble receptors in human disease

“…In these situations, the reason for having increased circulating soluble IL-2 receptor is uncertain and may represent a nonspecific response to inflammation or stress. Soluble IL-2 receptor levels in serum are often greatly elevated in patients with acute T cell leukemia/ lymphoma (ATLL) due to human T cell leukemia virus-1 (HTLV-1) [152]. In ATLL, the malignant cells have high expression of membrane-bound IL-2 receptors, so that the concentration of soluble IL-2 receptor in the serum is probably an indirect measure of tumor burden.…”