Prognostic value of serum soluble interleukin-2 receptor level in patients with diffuse large B cell lymphoma, treated with CHOP- or RCHOP-based therapy

Oki, Yasuhiro; Kato, Harumi; Matsuo, Keitaro; Kuwatsuka, Yachiyo; Taji, Hirofumi; Yamamoto, Kazuhito; Kagami, Yoshitoyo; Morishima, Yasuo

doi:10.1080/10428190802108888

Cited by 26 publications

(11 citation statements)

References 22 publications

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“…IL‐1R1 and sIL2R elevations were found associated with both polyclonal and monoclonal FLC. Many groups have found sIL2R elevations to be associated with an adverse prognosis in DLBCL . Serum IL12 is also recognized to be increased in DLBCL but was not a strong prognostic factor .…”

Section: Discussionmentioning

confidence: 99%

Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein‐10 predicts inferior prognosis in untreated diffuse large B‐cell lymphoma

et al. 2014

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The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long-term outcome in diffuse large B-cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow-up (monoclonal, EFS HR = 3.56, 95% CI: 1.88-6.76, p<0.0001; polyclonal, EFS HR = 2.56, 95% CI: 1.50-4.38, p=0.0006). 73% of DLBCL tumors with monoclonal FLC elevations were activated B-cell type (ABC) vs. 33% from patients with normal FLC. Only ABC-DLBCL lines secreted kappa FLC in vitro and this secretion could be inhibited by the NF-κB inhibitor bortezomib. Patients with monoclonal FLC had significantly (all p<0.001) elevated serum levels of IL-12, sIL-2Rα, IL-1R, and IP-10. Patients with polyclonal elevations of FLC had higher levels of IL-6 (p=0.033), IL-8 (p=0.025), sIL2Rα (p=0.011), and IL-1R1 (p=0.041). The combination of elevated FLC and a CXC superfamily chemokine IP-10 predicted a particularly inferior outcome characterized by late relapse. These elevated abnormal FLC and cytokines are potentially useful biomarkers for prognosis and selecting agents for untreated DLBCL.

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Section: Discussionmentioning

confidence: 99%

Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein‐10 predicts inferior prognosis in untreated diffuse large B‐cell lymphoma

et al. 2014

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“…( 3 ) 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 cleavage of IL‐2R, and its serum level rises in patients with some malignancies, including malignant lymphoma.…”

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confidence: 99%

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

et al. 2009

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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 ...

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“…Several previous reports revealed the importance of sIL-2Ra as a surrogate marker of tumor burden 9 or prognosis. [10][11][12][13][14] Although three reports [12][13][14] have suggested the clinical significance of sIL-2Ra in patients with DLBCL treated with rituximabcontaining chemotherapy, the rationale for this remains unclear. Furthermore, there have been no reports about the relationship between the level of sIL-2Ra and cell surface CD25 expression.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Importance of the Soluble Form of IL-2 Receptor^|^alpha; (sIL-2R^|^alpha;) and its Relationship with Surface Expression of IL-2R^|^alpha; (CD25) of Lymphoma Cells in Diffuse Large B-cell Lymphoma Treated with CHOP-like Regimen with or without Rituximab : A Retrospective Analysis of 338 Cases

Hashimoto

Yokohama

Saitoh

et al. 2013

J Clin Exp Hematopathol

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We evaluated the prognostic significance of the serum level of the soluble form of interleukin-2 receptorα (sIL-2Rα) and investigated its association with CD25 expression on tumor cells in diffuse large B-cell lymphoma (DLBCL). Three hundred and thirty-eight adult patients with newly diagnosed DLBCL were eligible for this retrospective study. 32.2% of patients were treated with CHOP-like regimen and 67.8% with R-CHOP-like regimen. CD25 expression on the surface of tumor cells was evaluated in 143 cases and its relationship with sIL-2Rα level was also investigated. Both overall survival (OS) and progression-free survival (PFS) were poorer in patients with higher sIL-2Rα, in both R-CHOP and CHOP groups. sIL-2Rα > 1,000 U/mL and performance status (PS) ≥ 2 were independently associated with poorer OS, and sIL-2Rα > 1,000 U/mL, age > 60 years, and ≥ 2 extranodal sites were independently associated with poorer PFS in the R-CHOP group. The sIL-2Rα level was higher in the CD25-positive group than in the CD25-negative group in stage 3 or 4 disease (p = 0.010). Multiple linear regression analysis showed CD25 expression to be independently correlated with sIL-2Rα levels. High sIL-2Rα is an important risk factor for survival in DLBCL treated with not only CHOP-like, but also R-CHOP-like regimens, regardless of the tumor's expression of CD25.

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Prognostic value of serum soluble interleukin-2 receptor level in patients with diffuse large B cell lymphoma, treated with CHOP- or RCHOP-based therapy

Cited by 26 publications

References 22 publications

Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein‐10 predicts inferior prognosis in untreated diffuse large B‐cell lymphoma

Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein‐10 predicts inferior prognosis in untreated diffuse large B‐cell lymphoma

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

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