CD25 (the alpha chain of the IL-2 receptor) has been shown to be expressed in hairy cell leukemia cells and a small subset of normal B cells. Recently, we reported that CD25 is expressed in a subset of diffuse large B-cell lymphoma (DLBCL) (ASH 2011 118:2666). However, its expression in follicular lymphoma (FL) has yet to be fully examined. The aim of this study was to clarify the clinical features of newly diagnosed CD25+ FL.
Eighty-four patients with newly diagnosed CD25+ FL who were admitted to our hospital between 2002 and 2012 were retrospectively evaluated. Biopsy specimens from lymph nodes or related tissues were analyzed by flow cytometry (FCM) using a combined method of single- and two-color staining. CD25 expression was defined as positivity of >20% of clonal B cells with CD19 or 20 expression >70% in a gated region. Results were compared with patients with reactive lymphadenopathy (n=27), DLBCL at initial presentation (n=91), and FL at relapse (n=13).
CD25 expression in untreated patients with FL (mean±SD, 10.6±9.9%; n=84) was almost equivalent to that in patients with reactive lymphadenopathy (mean±SD, 9.1±4.4%; n=27, P =0.3), and lower than that in untreated patients with DLBCL (mean±SD, 28.5±31.1%; n=91, P <0.001). There was a trend of a higher CD25 expression in biopsy specimens from relapsed FL than in those from newly diagnosed FL (mean±SD, 18.6±16.3 vs. 10.6±9.9%, respectively, P=0.077). With the sum of treated and untreated CD25+ FL, two-color FCM showed that the mean±SD of CD25/CD19 and CD25/CD20 dual expression was 28.5±26.5% (n=4) and 28±24.3% (n=4), respectively. The patients with newly diagnosed CD25+ (more than 20%) FL (n=10) showed some clinical features such as B symptoms (P =0.09), soluble IL-2 receptor titers of more than 5,000 U/ml (P =0.013), and advanced ages over 60 (P =0.16), compared with CD25- FL patients (n=74). Besides, there were some differences between CD25+ and CD25- FL in terms of histology grade 3 (50 vs. 32%, respectively, P=0.29) and the presence of t(14;18) (33 vs. 56%, respectively, P=0.27).Patients with FL at the initial presentation underwent rituximab-containing chemotherapy (n=68), radiotherapy (n=4), and observation (n=12). Kaplan–Meier analysis showed poorer progression-free survival (PFS) and overall survival (OS) in patients with CD25+ FL than that in patients with CD25- FL (2-year PFS, 36 vs. 82%, respectively, P <0.001; 6-year OS, 47 vs. 88%, respectively, P <0.01). Multivariate analysis revealed that CD25 expression is a significant prognostic factor for PFS (HR 6.4, 95%CI 2.4–17.4, P <0.001) and OS (HR 6.6, 95%CI 1.2–36.9, P= 0.027), which is independent of FLIPI score variables.
Newly diagnosed CD25+ FL may constitute a distinct subgroup associated with aggressive clinical features and an inferior prognosis. CD25 may be a new prognostic marker, and could be a therapeutic target in FL patients.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.