Abstract: To further clarify the histopathological findings of the floral variant of follicular lymphoma (FVFL), we studied 13 Japanese cases. Two histological subtypes of neoplastic follicles of FVFL have been described: (i) A macrogerminal center pattern where the mantle zone lymphocytes were invaginated into the neoplastic germinal center, often reminiscent of a floral design. (ii) A microgerminal center pattern where the massive invasion of mantle zone lymphocytes resulted in almost complete breakage of the neoplastic follicles. In the former pattern, the neoplastic germinal center usually contained large clusters of tumor cells, whereas in the latter, small clusters of up to 20 tumor cells or isolated tumor cells were observed in the neoplastic germinal centers. Moreover, occasional tumor cells showed a lymphocytic and/or histiocytic Reed‐Sternberg cell (L & H cells)‐like morphology. Both types of neoplastic follicles were observed to a varying degree in most cases. The macrogerminal center pattern was predominant in nine cases (70%), whilst the microgerminal center pattern was predominant in only four cases (30%). Three lesions (23%) had a marginal zone component. Immunohistochemistry showed that atypical follicular center cells, including L & H cells, were CD3−, CD5−, CD10+, CD20+, CD43−, bcl‐2+, cyclinD1−. The overall histological findings of the macrogerminal center are similar to those of florid progressive transformation of germinal center (PTGC), whilst the microgerminal center pattern is similar to that of nodular lymphocyte‐predominant Hodgkin lymphoma. Initially, the differential diagnosis between FVFL and florid PTGC was emphasized. However, the present study indicates that nodal marginal zone B‐cell lymphoma possessing floral follicles and nodular lymphocyte‐predominant Hodgkin lymphoma should be added to the differential diagnosis of FVFL. The germinal center B‐cell nature of FVFL is most clearly recognizable by immunohistochemistry, though histological appearance alone may cause some diagnostic problems.

Abstract: Abstract 3948 Background: The central nervous system (CNS) is considered a sanctuary because drugs at standard doses rarely reach it. CNS event is defined as disease recurrence in the CNS during complete systemic remission or CNS progression as concurrent disease in the CNS during active systemic disease. These CNS events are associated with extremely poor patient prognosis. To evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab (R) era, we performed a retrospective study with a large cohort in Japan. Materials and Methods: All patients were diagnosed as having DLBCL and underwent primary therapy from September 2003 to December 2006. Patients with distinct forms of DLBCL, such as intravascular lymphoma, primary effusion lymphoma, and pyothorax-associated lymphoma were excluded. Those who had received any prophylactic CNS treatment; and those with CNS involvement at the beginning of therapy were also excluded. Primary therapy comprised standard R-CHOP therapy or R-THP-COP therapy (pirarubicin instead of doxorubicin hydrochloride). CNS involvement was considered when malignant cells were detected in cytocentrifuged preparations of cerebrospinal fluid (leptomeningeal type) and/or when an intracranial or spinal mass was detected by radiologic imaging such as computed tomography or magnetic resonance imaging (parenchymal type). Results: (1) Baseline characteristics. Clinical data from 1,492 patients were collected from 48 institutions. The median age was 67 years (range, 15–93 years). R-CHOP therapy was administered in 1,227 patients (82.2%) and R-THP-COP therapy, in 265 patients (17.8%). Therapy for 6–8 cycles was administered to 1099 patients (73.7%). Local irradiation was included for 344 patients (23.1%). The 5-year overall survival (OS) rate in the entire cohort was 72.8%, and the median observation period for the surviving patients was 47.6 months. (2) Incidence of CNS events. In total, 94 CNS events (6.3%) were recorded. More than half were of the parenchymal type (57.4%); the rest were mostly of the leptomeningeal type (29.8%), and some were of both types (12.8%). The events occurred during the first complete remission (CR) in 40 patients (42.6%) and in the second or later CR in 11 patients (11.6%). Death from any cause was recorded in 64 of the 94 patients (68.1%) during the observation period, and most deaths were due to lymphoma. The cumulative 5-year probability of CNS events was 8.0%. (3) Risk factors for CNS events. Multivariate Cox regression analysis identified involvement of the breast (relative risk (RR), 7.9), adrenal gland (RR, 3.3), paranasal sinus (RR, 2.9), and bone (RR, 2.3). as risk factors for CNS events. Time to CNS event curves differed significantly between patients with and without CNS risk sites (P 〈 0.001). (4) Survival after CNS events. Patients with CNS events demonstrated significantly poorer OS (P 〈 0.001). The 2-year OS rate after a CNS event was 25.7%, and the 50% survival duration was 4.6 months. No significant differences were observed between any 2 of the 3 types of CNS events. Depending on the systemic lymphoma status at the time of the CNS events, patients in first CR showed better survival than the others (P = 0.019). Patients in any CR also showed superior survival than those not in CR (P = 0.015). Conclusions: We concluded that DLBCL patients in the R era with any of these risk factors (breast, adrenal gland, paranasal sinus, or bone involvement), in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events. The efficacy and manner of CNS prophylaxis for each involvement sites should be evaluated further. Disclosures: No relevant conflicts of interest to declare.

Abstract: Abstract 1935 Poster Board I-958 Introduction: Several reports have identified soluble-form IL-2 receptor á (sIL-2Rá) as a significant prognostic factor in patients with non-Hodgkin lymphoma treated using chemotherapy, particularly in rituximab-containing regimens. However, the clinical significance of sIL-2R is not fully understood, as only small populations have been studied to date. The rationale for increasing of serum level of sIL-2Rá in non-Hodgkin lymphoma is also unclear. Patients and Methods: We analyzed 409 patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2001 and July 2008. Treatment comprised CHOP-like regimen with (R-CHOP-like) or without rituximab. Levels of sIL-2R were evaluated with enzyme-linked immunosorbent assay at diagnosis. Overall survival (OS) and progression-free survival (PFS, death from any cause, relapse and refractory disease) were analyzed using Kaplan-Meier methods and survival was compared using log-rank tests. To estimate the survival impact of several factors, including sIL-2Rá level, PS, LDH, B symptoms, extranodal sites ≥2 and age, we performed multivariate analysis using Cox proportional hazards. In 166 of 409 patients, CD25 (IL-2Rá) expression on tumor cells was evaluated using a lymphoma sample from the lymph node, bone marrow, blood or other extranodal organ by flow cytometry. To estimate CD25 expression of tumor cell, CD45 bright cells (mature lymphocyte gate) were gated and considered positive if positivity was seen in 〉 20% of the population excluding CD4-positive cells) using three-color flow cytometry. Results: Median age was 68 years (range, 17-91 years), males/females 1.18, and 28.9% of patients were treated with CHOP-like regimen and 60.2% with R-CHOP-like regimen. Clinical stage was I in 24.4%, II in 24.2%, III in 13.1%, and IV in 38.8%. International Prognostic Index (IPI) was Low in 33.5%, LI in 23.5%, HI in 18.7% and H in 24.3%. Median follow-up for CHOP-like and R-CHOP-like groups was 924 days (range, 16-2878 days) and 799 days (range, 29-2688 days), respectively. Median sIL-2Rá value was 1360 U/L (range, 170-59,500 U/L). For the entire population, CR rate was 71.9%, 3-year OS was 67.6% and PFS was 58.8%. OS differed significantly between sIL-2R 〉 1000 U/L and ≤1000 U/L, between 〉 2000 U/L and ≤2000 U/L and between 〉 3500 U/L and ≤3500 U/L, (p 〈 0.001, 〈 0.001, 〈 0.001, respectively). PFS also differed at each sIL-2Rá point (p 〈 0.001, respectively). The sIL-2Rá value correlated moderately or well with other prognostic factors, such as LDH, PS ≥2, B symptoms, ≥2 extranodal lesions, age and clinical stage by Spearman correlation analysis (r=0.579, 0.258, 0.404, 0.474, respectively). Multivariate analysis showed sIL-2Rá as a significant prognostic factor, in addition to several factors. In a group treated with R-CHOP-like regimen, 3-year OS was 74.5% and PFS was 68.8%. OS again differed significantly between sIL-2Rá 〉 1000 U/L and ≤1000 U/L, between 〉 2000 U/L and ≤2000 U/L and, between 〉 3500 U/L and ≤3500 U/L (p 〈 0.001, respectively). PFS was also significant at each sIL-2Rá value. The higher the level of IL-2R, the worse the 3-year OS at each sIL-2R value (63.6%, 60.1%, 53.2%, respectively). However, we could not identify statistical significance of sIL-2 level by multivariate analysis. IL-2Rá usually functions as a cytokine receptor on cell surface, called CD25. To show the importance of CD25 expression in lymphoma cells on serum level of soluble form IL-2Rá, we compared sIL-2Rá levels in CD25-positive and -negative cases. CD25-positive cases showed significantly higher sIL-2Rá level than CD25-negative cases among the overall population. After defining two group according to clinical stage (I+II and III+IV), sIL-2Rá level was higher in the CD25-positive group than in the CD25-negative group for the stage III+IV group (p=0.001), but this difference was not seen for the stage I+II group (p=0.390). This trend was also seen in the case of IPI, L+LI (p=0.642) and HI+H (p=0.0016)). These results suggest that one rationale for increasing level of sIL-2Rá in DLBCL is removing from tumor cell like other cytokine receptor. Conclusion: In terms of survival and relapse, sIL-2R remains an important risk factor of DLBCL, not only in CHOP-like regimens, but also in the R-CHOP era. The survival rate of patients with sIL-2Rá 〉 3500 U/L is extremely poor even if treated with R-CHOP (53.2%). We showed that one rationale for increasing level of serum sIL-2Rá level in DLBCL is to remove from the tumor cell surface. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction The prognosis of classic Hodgkin lymphoma (cHL) in young adults has improved following advances in current therapeutics. However, evidence of elderly patients with cHL has limited due to its rarer. To analyze clinical outcomes and risk factors in elderly patients with advanced-stage cHL who received a doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen, we conducted a nationwide multi-center retrospective study in Japan (UMIN000033264). Methods The key eligibility criteria of the current study were as follows: 1) patients with histologically diagnosed cHL between 2007 and 2016 in each institution; 2) advanced-stage cHL (stage III, IV or IIB with bulky or extranodal lesion); 3) age at diagnosis & gt; 60 years; and 4) had received at least one cycle of an ABVD regimen as initial treatment including a modified ABVD regimen (dacarbazine dose reduced to 250 mg/m 2 at first cycle). Patients with human immunodeficiency virus infection or methotrexate-associated cHL were excluded. The primary endpoint was 5-year overall survival (OS). Secondary endpoints included progression-free survival (PFS) and event-free survival (EFS), the latter defined as the time from a diagnosis of cHL to disease progression or relapse, subsequent systemic chemotherapy for cHL, or death due to any cause in this study. The average relative dose intensity (ARDI) of ABVD was calculated as the sum of the relative dose intensity of each drug divided by four. Results A total of 171 patients from 45 institutions were included in this study. The central pathological review could be performed in 140 cases (82%), in which histological subtypes of cHL were determined as follows: mixed cellularity, 89 (64%); nodular sclerosis, 33 (24%); lymphocyte-deleted, 4 (3%); lymphocyte-rich, 2 (1%); not otherwise specified, 12 (9%). The median age was 71 years (interquartile range [IQR] 65-76). The number of patients in each 10-year age group was 79 (46%) for 61-70 years, 78 (46%) for 71-80 years, and 14 (8%) for & gt; 81 years. The numbers of patients with ECOG performance status (PS) ≥2 and B symptoms were 33 (19%) and 85 (50%), respectively. Bulky mediastinal diseases were found in four patients (2%). The risk factors used for the International Prognostic Score (IPS), including male sex, stage IV, hypoalbuminemia, anemia, leukocytosis, and lymphopenia, were not significantly different among these age groups. The median number of cycles of ABVD was 6 (IQR:5-7), and 66% of patients completed at least 6 cycles. The median ARDI was 77%. The median ARDI in each 10-year age group was 88% for 61-70 years, 71% for 71-80 years, and 54% for & gt; 81 years. With a median follow-up time of 52 months (IQR:31-76), the estimated OS, PFS, and EFS at 5 years were 72%, 59%, and 54%, respectively. Among 131 patients whose Epstein-Barr virus (EBV) status was analyzed using EBV-encoded small RNA1 (EBER1) in situ hybridization, 61 (46%) were positive for EBER1. The OS was not significantly different between EBV-positive and EBV-negative patients (75% and 76% at 5 years, respectively). Univariate analysis for OS revealed that age, PS ≥ 2, hypoalbuminemia, anemia, lymphopenia, and the presence of B symptoms were significantly associated with short OS. In multivariate analysis, age (hazard ratio [HR] 1.568 per 10-year increase, 95% confidence interval [CI] 1.020-2.411) was only an independent risk factor for OS, whereas lymphopenia (HR 1.967, 95% CI 1.196-3.235) was an independent risk factor for EFS. Higher ARDI was significantly associated with improved OS and EFS. Bleomycin-induced lung toxicity (BLT), observed in 41 (24%) patients, was not associated with OS. In this study, we found that 55 patients died: 23 within two years after diagnosis mainly due to cHL progression (n = 10, 43%) and treatment-related toxicity (infection [n = 4, 17%] and BLT [n = 4, 17%] ). The remaining 32 patients died more than two years after diagnosis mainly due to second primary malignancies (n = 14, 44%), including solid tumors (n = 6), other types of lymphoma (n = 4), and myelodysplastic syndrome/acute myeloid leukemias (n = 4). Conclusions The HORIZON study showed relatively good prognosis for elderly patients with advanced-stage cHL who received an ABVD regimen (estimated five-year OS rates was 72%). Age and lymphopenia were an independent risk factors for OS and EFS, respectively. The development of novel therapies is warranted to improve the outcomes of such patients. Disclosures Makita: SymBio: Honoraria; Novartis: Honoraria; Eisai: Honoraria; Daiichi-Sankyo: Consultancy; CSL Behring: Honoraria; Chugai: Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kusumoto: Kyowa Kirin: Honoraria; Chugai: Honoraria, Research Funding; Daiichi Sankyo: Research Funding. Tsujimura: Takeda: Honoraria; Chugai: Honoraria; Kyowa Kirin: Honoraria; Eisai: Honoraria; Janssen: Honoraria. Takayama: Chugai: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding. Kuroda: Otsuka Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Abbvie: Consultancy, Honoraria; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Sysmex: Research Funding; Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Shionogi: Research Funding; Asahi Kasei: Research Funding; Taiho Pharmaceutical: Research Funding; Fujimoto Pharmaceutical: Current Employment, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-MyersSquibb: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical K.K: Consultancy. Shimada: BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Chugai: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; AstraZeneca: Honoraria; Otsuka: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; SymBio: Honoraria. Okamoto: Chugai: Research Funding; Kyowa Kirin: Research Funding; Ono: Research Funding; Taiho: Research Funding; Takeda: Research Funding. Asano: Takeda: Honoraria. Maruyama: Janssen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Research Funding; MSD: Honoraria, Research Funding; Otsuka: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Astellas Pharma,: Research Funding; Celgene: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Amgen: Research Funding; BMS: Honoraria, Research Funding; Mundipharma: Honoraria; Kyowa Kirin: Honoraria; Zenyaku: Honoraria; AstraZeneca: Honoraria; Nippon: Honoraria; SymBio: Honoraria. Yamaguchi: Chugai: Honoraria, Research Funding; Genmab: Research Funding; MSD: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Takeda: Honoraria; Ono: Honoraria; Celgene: Honoraria; Otsuka: Honoraria; Sumitomo Dainippon: Honoraria; Eisai: Honoraria; AstraZeneca: Consultancy. Nagai: AbbVie: Research Funding; AstraZeneca: Honoraria, Research Funding; Bayer: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Chordia Therapeutics: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Kyowa Kirin: Research Funding; Mundipharma: Honoraria, Research Funding; Nippon Shinyaku: Research Funding; Novartis: Honoraria; Ono Pharmaceutical: Honoraria; Sanofi: Honoraria; Sumitomo Dainippon Pharma: Honoraria; SymBio Pharmaceuticals: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Zenyaku Kogyo: Research Funding.

Abstract: Background: Analysis of prognostic factors and clinical trials of novel agents for Waldenstrӧm macroglobulinemia (WM) are ongoing in Western countries, but few studies of WM have been performed in Japan. As a step toward future investigations, we retrospectively analyzed clinical features and prognostic factors in Japanese patients with WM. Methods: We retrospectively analyzed clinical and laboratory characteristics, treatment and outcomes of 110 patients with WM, IgM-MGUS or lymphoplasmacytic lymphoma (LPL) diagnosed from January 2001 to March 2013 at 12 institutes. Overall survival (OS) was analyzed using Kaplan-Meier methods and survival was compared using log-rank testing. Several clinical characteristics at diagnosis were assessed by Cox regression for uni- and multivariate analysis for OS. Results: Median age at diagnosis was 69 (range, 41-96) years, 73.6% were male, 12.0% had an ECOG performance status 2-4 and 6.4% presented with B-symptoms. Hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia and cold agglutinin disease were shown in 9.1%, 4.5%, 1.8%, 4.5% and 2.7%, respectively. In 94 patients with available CT findings at diagnosis, lymphadenopathy, hepatosplenomegaly, pleural effusion, lung involvement, bone involvement and skin involvement were shown in 41.5%, 14.9%, 8.5%, 4.3%, 4.3% and 6.4%, respectively. Median serum monoclonal protein level was 2.62 g/dl (range, 0.70-9.35 g/dl). Symptomatic WM was present in 76 patients, asymptomatic WM in 23 and IgM-MGUS in 2 according to criteria of the Second International Workshop on WM. Seven patients showed IgG- or IgA-secreting LPL and 2 showed LPL without bone marrow infiltration. In patients with symptomatic WM, international prognostic scoring system for WM (ISSWM) was low in 9.2%, intermediate in 34.2%, high in 39.5% and unknown in 17.1%. Among patients with asymptomatic and symptomatic WM, watchful waiting was performed in 91.3% and 40.0%, respectively, with 61.9% and 36.7% remaining untreated, respectively. Median time to treatment from diagnosis of asymptomatic or symptomatic WM was 240 days (range, 3-1238 days) and 31 days (range, 0-2011 days), respectively. Oral alkylating agents were administered to 34.7% of patients with WM, 19.4% were treated with CHOP or CHOP-like regimen with or without rituximab, 8.2% received fludarabine mono- or combination therapy and 6.1% received rituximab monotherapy. Rituximab-containing therapy was administered as the initial treatment in 33.8% of patients who received treatment. Overall response rate (ORR) (complete + partial response rate) was 48.6%, and patients treated with rituximab-containing therapy displayed higher ORR (64.0%) compared to those with non-rituximab therapy (40.8%). Plasmapheresis was performed in 3.7% of patients. Three patients (2.7%) showed transformation to diffuse large B-cell lymphoma, and 7 (6.4%) developed second primary malignancies. Median follow-up was 38 months, 5-year OS rate for all patients was 74.9% (95% confidence interval (CI) 62.5-83.7) and rates for those with symptomatic WM, asymptomatic WM and other LPL were 66.0% (95%CI 50.6-77.6), 100% and 88.9% (95%CI 43.3-98.4), respectively. Significant differences in survival between risk groups of ISSWM in patients with symptomatic WM were not seen (5-year OS: high, 62.4%; intermediate, 64.3%; low, 75.0%; p=0.86). Although no significant difference in OS was observed compared to initial treatment (p=0.265), patients treated with rituximab during the observation period showed significantly prolonged OS compared to those treated without rituximab (5-year OS rates: 78.9% vs. 45.6%, p=0.036). In univariate analysis, age, pleural effusion, serum albumin, C-reactive protein and serum IgM levels were poor prognostic factors for OS. In multivariate analysis, age 〉 65 years (hazard ratio (HR)=3.294; 95%CI 1.097-9.888, p=0.0336) and pleural effusion (HR=4.55; 95%CI 1.602-12.930, p=0.0045) were identified as significant prognostic factors for OS. Conclusion: Prognostic factors for WM in Western countries may not be applicable to Japanese patients. This study suggested presence of pleural effusion at diagnosis is associated with poor clinical outcomes. Further investigations including histopathological examinations and molecular analyses are required to elucidate prognostic factors in Japan. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction: Soluble-form IL-2 receptor α (sIL-2Rα) has been identified as a significant prognostic biomarker in patients with non-Hodgkin’s lymphoma (NHL) treated using rituximab-containing regimens. However, the clinical significance of sIL-2R is not fully understood, especially in subtypes of NHL, such as follicular lymphoma (FL). In addition to sIL-2Rα, β2-microglobulin (B2M) has been used as a prognostic and diagnostic biomarker of FL. We compared the predictive and diagnostic abilities of sIL-2Rα and B2M for FL. Patients and Methods: We analyzed 305 patients newly diagnosed with FL (Grade1-3a) between January 2001 and July 2012. Levels of sIL-2Rα and B2M were evaluated at diagnosis. The optimal cut-off values of sIL-2Rα and B2M were calculated from receiver operating characteristic (ROC) curves. Overall survival (OS) and progression-free survival (PFS, death from any cause, relapse and refractory disease) were analyzed using Kaplan-Meier methods and survival was compared using log-rank tests. To estimate the survival impact of several factors including sIL-2Rα, B2M, Hb 〈 12g/dl, B symptoms, LDH, bone marrow involvement, bulky disease, extranodal disease and age, we performed multivariate analysis using the Cox proportional hazards model. Results: Median age was 59 years (range: 28-86 years) and the male: female ratio was 1:1. Most (245/305) patients were treated with chemotherapy regimens. Rituximab was concomitantly administered to 227 of these patients (R-Chemo) and 52 of these patients received rituximab maintenance for 2 years. In the 305patients, clinical stage was I in 12.3%, II in 15.1%, III in 24.9%, and IV in 45.9% and the Follicular Lymphoma Prognostic Index was low in 35.7%, intermediate in 27.2% and high in 36.7%. The median follow-up period was 1,516 days (range: 7 - 4,776 days). The median sIL-2Rα value was 1,107.5 U/L (range: 127-20,800 U/L) and the median B2M value was 2.2 mg/L (range: 1.0-10.29). The 3-year OS of the entire population was 87.8% and the 3-year PFS was 65.1%. The percentage of patients whose sIL-2Rα or B2M level was higher than the upper normal limit (520 U/L for sIL-2Rα, 2.0 mg/L for B2M) at diagnosis was higher for sIL-2R (76.8%) than for B2M (54.2%) patients (p 〈 0.0001), indicating that sIL2Rα is more sensitive diagnostic marker for FL than B2M. To estimate the predictive value of sIL-2Rα and B2M for survival, we determined the optimal cut-off levels of sIL-2Rα and B2M using ROC analysis. This analysis showed that sIL-2Rα and B2M values of 1,700 U/L and 2.2mg/Lrespectivelywere the most sensitive and specific values for prediction of a 3-year PFS. Using these values, patients were separated into two significantly different groups of sIL-2Rα values ( 〉 1,700 U/L and ≤1,700 (p 〈 0.0001)) and of B2M values ( 〉 2.2 mg/L and ≤ 2.2 mg/L (p=0.0017)). Further, PFS differed significantly between patients with sIL-2Rα values of 〉 520 U/L and ≤520 U/L, 〉 1,000 U/L and ≤1,000 U/L ,and 〉 2,000 U/L and ≤2,000 U/L (p=0.03, 0.0003 and 〈 0.0001, respectively) and also between patients with B2M values of 〉 2.0 mg/L and ≤2.0 mg/L, 〉 2.5 mg/L and ≤2.5 mg/L, 〉 3.0 mg/L and ≤3.0 mg/L (p=0.011, 0.0016 and 0.0184, respectively). Univariate analysis identified several reported prognostic factors, such as clinical stage3-4, B2M 〉 2.2 mg/L, number of nodal site 〉 5, bone marrow involvement, Hb 〈 12 g/dl, performance status 〈 2, number of extranodal site 〉 1, longest diameter 〉 6 cm ( 〈 0.0001, 0.002, 0.0002, 0.0204, 0.0345, 0.0089, 0.0004 and 0.0053, respectively) in addition to sIL-2Rα (p 〈 0.0001). Cox multivariate analysis indicated sIL-2Rα as a significant prognostic factor (p=0.0361), in addition to several other factors (bone marrow involvement, number of extranodal site 〈 2, number of nodal site 〉 5). In the group treated with the R-chemo regimen, the 3-year OS was 86.9% and the 3-year PFS was 64.9%. Within this group, PFS significantly differed between the two groups of sIL-2Rα; 〉 1,700 U/L and ≤1,700 (p 〈 0.0001), and between two groups with different B2M values 〉 2.2 mg/L and ≤ 2.2 mg/L (p=0.0056). Again, multivariate analysis showed that sIL-2Rα ( 〉 1,700 U/L), in addition to several other factors, was associated with poorer prognosis. Conclusion: This study showed that sIL-2Rα is a more sensitive diagnostic biomarker of FL than B2M. In terms of survival, sIL-2R is an important risk factor of FL, not only for all patients with FL, but also in the R-Chemo era. Disclosures Handa: Celgene: Research Funding; Yakult: Research Funding; Kirin: Research Funding; Chugai: Research Funding.