Serum soluble interleukin‐2 receptor level and immunophenotype are prognostic factors for patients with diffuse large B‐cell lymphoma

Abstract

Diffuse large B-cell lymphoma is the most common form of nonHodgkin lymphoma. Although many studies have attempted to identify prognostic factors, most have focused on conventionally treated patients. The influence of anti-CD20 antibody (rituximab) should be considered now. We evaluated the prognostic significance of serum soluble interleukin-2 receptor levels and germinal center Bcell-like or non-germinal center B-cell like subgroups in 80 patients with diffuse large B-cell lymphoma, who had been treated with rituximab. Serum soluble interleukin-2 receptor levels ranged from 322 to 39900 U/mL (median 1365 U/mL). Sixteen (20%) were germinal center B-cell-like subgroups, and the remainder (80%) non-germinal center B-cell-like. Survival analysis associated lower serum soluble interleukin-2 receptor level and germinal center B-cell-like phenotype with better overall survival (P = 0.015), whereas multivariate analysis, including International Prognostic Index factors, revealed that only higher performance status score and higher serum lactate dehydrogenase levels significantly affected survival. However, serum soluble interleukin-2 receptor levels were elevated in patients with higher International Prognostic Index scores as well as in the nongerminal center B-cell-like subgroup. Serum soluble interleukin-2 receptor levels, International Prognostic Index, and subphenotypes were strongly correlated with each other. Our study showed that soluble interleukin-2 receptor is quite useful and may serve as a substitute for the International Prognostic Index, especially for patients undergoing treatment. Moreover, the differentiation between the germinal center B-cell-like and non-germinal center B-cell-like phenotypes is also useful for predicting patients with diffuse large B-cell lymphoma, even among those treated with rituximab. (Cancer Sci 2009; 100: 1255-1260) D iffuse large B-cell lymphoma (DLBCL) is one of the most common subtypes of non-Hodgkin lymphoma (NHL), representing 30% to 40% of adult cases of NHL, and its incidence has increased in the past few decades. DLBCL is recognized clinically and biologically as a heterogeneous group of tumors.(1) Recently, therapeutic methods have also improved. In particular, anti-CD20 antibody (rituximab) is now the most powerful tool for B-cell malignancies.Many investigators have reported on the prognostic factors of NHL, and the most powerful one we have recognized is the International Prognostic Index (IPI).(2) The IPI contains patients' age, performance status (PS), Ann Arbor clinical stage (CS), serum lactate dehydrogenase (LDH) activity, and the number of extranodal lesions. In addition, in the rituximab era, a revised IPI has been proposed, which is better than the standard IPI. Several reports have revealed that serum soluble interleukin-2 receptor (sIL-2R) level may also be a prognostic factor for NHL.(4-6) IL-2R is expressed not only on the surface of activated T or B lymphocytes, but also on parts of lymphoid malignancies. sIL-2R is released from the cell membrane by ...

Soluble Interleukin 2 Receptor-Alpha (sIL-2Rα) in the Peripheral Blood of Dogs—Comparison of Malignant Neoplasia with Other Diseases

“…In contrast to human medicine, where sIL-2Rα is an already established marker for malignant lymphoma [9,16,23], we could not find evidence that sIL-2Rα is a useful marker for detecting malignant lymphoma in dogs. Although there were only two dogs with malignant lymphoma it is noticeable that only one of the dogs showed detectable sIL-2Rα in serum: it was the highest serum level of the dogs in the malignant neoplasia group (71.8 pg/ml) which lay remarkably lower than the highest serum levels in the nonneoplastic/benign tumor group.…”

“…It is an interesting fact that sIL2-Rα is an established marker in human medicine for diagnosis and progression of many tumorous diseases [6,8,9,23], but does not have huge relevance as a marker for inflammation in non-tumorous diseases. There are two exceptions: rheumatoid arthritis [24] and human visceral leishmaniasis [18].…”

Soluble IL-2Rα facilitates IL-2–mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma

“…In B-cell NHL, especially those with an aggressive phenotype, serum levels of sIL-2R␣ were elevated and correlated with a poor outcome. [28][29][30] This also holds true in patients after treatment with CHOP or R-CHOP, 36,37 strongly suggesting a prognostic value of serum sIL-2R␣ levels. Our finding that serum levels of sIL-2R␣ were elevated and correlated with a poor prognosis in FL patients is the first report in this histologic group and is in agreement with the above reports.…”

“…[28][29][30] It is unknown in FL whether sIL-2R␣ is present in patient serum and can serve as a prognostic factor. Moreover, the biologic relevance of sIL-2R␣ is completely unknown particularly in terms of whether sIL-2R␣ has an impact on IL-2-mediated functions An Inside Blood analysis of this article appears at the front of this issue.…”

Germinal Center B-Cell-Like versus Non-Germinal Center B-Cell-Like as Important Prognostic Factor for Localized Nodal DLBCL

“…[19][20][21] In particular, a high LDH titer is detected in nodal lymphomas at a greater frequency than in extranodal lymphomas. 4 In the present study, LDH titer levels were within the normal range in 82% of the patients.…”