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Introduction Ocular adnexal lymphomas (OALs) are relatively rare, accounting for 2% of all lymphomas and 5% of non-Hodgkin lymphomas. OALs often represent as isolated and require only radiation therapy (RT). However, some of them are systematic and need intensive chemotherapy. Methods We analyzed newly diagnosed OALs at Cancer Institute Hospital from January 2006 to May 2013. All patients (pts.)’ samples were performed biopsy by expert oncology-ophthalmologists and all the histopathology samples were reviewed by expert hematopathologists, according to the WHO classification. Positron emission tomography-computed tomography and bone marrow assessment were required for initial evaluation. Results A total of 83 pts. were included in this study. Baseline pts.’ characteristics were a median age of 64.48 years (range, 29.46-85.26 years), 39 male and 44 female, 62 pts. (74.7%) with stage I (according to Ann Arbor staging system), and 21(25.3%) with over stage II. Sixty-five pts. (78.3%) had unilateral OAL, and 18 (21.7%) bilateral. None had central nervous system involvement. Sixty pts. (72.3%) had extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, in which 9 pts. with over stage II, 9 pts. (10.9%) diffuse large B cell lymphoma (DLBCL), 3 pts.(3.6%) follicular lymphoma, 2 pts.(2.4%) mantle cell lymphoma, and 9 pts. (10.8%) others. Fifty-five pts.(66.3 %) have received only RT, 19 pts.(22.9%) only chemotherapy, 5 pts.(6.0%) both RT and chemotherapy, and 4 pts. (4.8%) haven’t received any therapy at the hospital. Nineteen pts. have received rituximab with or without other chemotherapy. At a median follow-up of 26.8 months (range 1.3-88.7), the 2-year progression free survival (PFS) and overall survival (OS) rates were 84.0% and 91.6%, respectively. In MALT, PFS and OS were 96.2% and 95.0%, respectively. In DLBCL, PFS and OS were 37.5% and 66.7%, respectively. The sites were orbit (38, 45.8%), conjunctiva (32, 38.6%), lachrymal gland (7, 8.4%), eyelid (5, 6.0%), and dacryocyst (1, 1.2%). None demonstrated disease progression at conjunctiva. Three pts. (60.0%) at eyelid were progressive, 3 pts. (42.9%) at lachrymal gland, and 6 pts. (15.7%) at orbit. Over stage II contained 13 pts. at orbit, 3 pts. at conjunctiva and eyelid, and 2 pts. at lachrymal gland. DLBCL were 6 pts. at orbit, 1 pt. at conjunctiva, eyelid, dacryocyst, and lachrymal gland. Conclusions MALT demonstrated good prognosis. DLBCL as OALs might indicate poorer prognosis than those at other parts. At the standpoint of site, conjunctiva represented remarkably good prognosis. Conjunctiva may be independent from other OALs. Eyelid and lachrymal gland represented high rate of progressive disease. For ophthalmologists, especially the back side of bulbar is hard to distinguish between conjunctiva and eyelid. The separation of both at biopsy is important because the prognoses of them are different. Since the sample of biopsy is small at OALs, careful collection of sample by ophthalmologists and choice of examination by hematopathologists are important. OALs require cross-sectional cooperation for diagnosis and treatment. Disclosures: Yokoyama: Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy.

Abstract 1611 Background: Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a recognized a rare distinct entity strongly associated EBV infection, accounting for 3% to 10% of malignant lymphomas in East Asia. Recent studies suggest that concurrent chemoradiotherapy was effective as first-line therapy for patients with localized ENKL, nasal type. We assess treatment results with concurrent chemoradiotherapy for ENKLs. Patients and methods: From December 2007 to July 2010, newly diagnosed localized ENKL, nasal type, and treated with concurrent radiotherapy (median 50 Gy; range 46–56 Gy) and 3 cycles of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) at the Cancer Institute Hospital, Tokyo, Japan were analyzed retrospectively. All the histopathological samples were reviewed according to the WHO classification by expert hematopathologists. Results: Total of sixteen patients was identified. Baseline patients. characteristics included a median age of 56.5 years (range; 30–76 years), eleven men and five women, thirteen patients (81%) with stage IE and three (19%) with stage IIE. For IPI, patients with low and low-intermediate risks were thirteen patients (81%) and three (19%), respectively. For NKIPI, patients with group 1, 2, and 3 were six patients (37%), seven (44%), and three (19%), respectively. All patients received concurrent chemoradiotherapy, and eleven patients (69%) achieved complete remission, with 2 partial remissions. The overall response rate was 81%. At a median follow-up of 17 months (range; 2–44), the 2-year progression-free survival and overall survival rates were 54.7% and 61.1%, respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. Grade 3/4 adverse events were leukopenia (100%), neutropenia (100%), anemia (19%), mucositis (63%), anorexia (81%), and febrile neutropenia (25%), respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. No treatment-related deaths were observed. Conclusions: Concurrent radiotherapy and DeVIC for patients with localized ENKL, nasal type, demonstrated favorable outcomes. We are now investigating what factors indicate good or poor prognosis in this regimen. Progression free survival of concurrent radiotherapy and DeVIC regimen Disclosures: Yokoyama: CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy. Mishima:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy.

Abstract 3659 Introduction Prognostic predictors for newly diagnosed malignant lymphoma, such as International Prognostic Index (IPI), reversed-IPI, Follicular Lymphoma International Prognostic Index (FILIP), and Prognostic Index for peripheral T-cell lymphoma (PIT), are well known. On the other hand, prognostic factors for recurrent or refractory malignant lymphoma have never been reported. Patients and methods We retrospectively analyzed patients with recurrent or refractory malignant lymphoma treated with ICE or DHAP as salvage treatment from April 2005 to June 2010 in our institute. We evaluated five biological parameters; C-reactive protein (CRP), lactate dehydrogenase (LDH), hemoglobin (Hb), beta 2 microglobulin (ƒÀ2m), and soluble interleukin 2 receptor (sIL-2R) before salvage treatment. The cut-off of CRP, LDH, and ƒÀ2m was defined with upper normal limit, that of Hb was defined with lower normal limit, and that of sIL-2R was defined with 1000 IU/L. Primary endpoint was overall survival (OS) after salvage treatments were started. OS was analyzed by Kaplan-Meier method. Biological prognostic factors for OS were evaluated by Cox regression analysis. All reported p values were two-sided, and p Results 69 patients with recurrent or refractory malignant lymphoma were entered into this study; 50 with recurrent lymphoma, and 19 with refractory lymphoma. On histological examination, 41 were diffuse large B-cell lymphoma (DLBCL), 8 were peripheral T-cell lymphoma-not otherwise specified, 6 were Hodgkin's lymphoma, 6 were angioimmunoblastic T-cell lymphoma, 4 were NK lymphoma, 2 were ALK-negative anaplastic large cell lymphoma, and 2 were follicular lymphoma grade 3b. Median level of CRP, LDH, Hb, ƒÀ2m, and sIL-2R were 0.3 IU/L (range, 0.1 – 26.7 IU/L), 241 IU/L (range, 130 – 6510 IU/L), 11.8 g/L (5.0 – 15.8 g/L), 2.01 IU/L (range, 1.1 – 4.44 IU/L), and 970 IU/L (range, 275 – 7840 IU/L), respectively. 53 patients and 16 patients received ICE and DHAP, respectively. 28 patients were treated with salvage treatment combined with rituximab. After a median follow-up time of 12.3 months (range, 1.3 – 70.8), median OS was 15.6 months (95% CI, 10.6 – 20.6), and there was no significant difference between the ICE arm and the DHAP arm (17.6 months vs 13.6 months, respectively; p =.100). The OS was significantly worse in patients with the following parameters: elevated CRP level (hazard ratio 3.847; p =.015), elevated LDH level (hazard ratio 3.972; p =.009), and anemia (hazard ratio 3.847; p =.014) according to the multivariate analysis. When outcome was plotted according to the numbers of elevated CRP level, elevated LDH level and anemia before salvage treatment, three risk groups emerged. Patients with zero prognostic factors have the best outcome, patients with one or two prognostic factors have moderate outcome, and patients with three prognostic factors have the poorest outcome. We defined these as low risk (L-R), intermediate risk (I-R), and high risk groups (H-R), respectively. The median OS of H-R, I-R, and L-R were 4.7 months (95% CI, 2.1 – 7.3), 17.6 months (95% CI, 12.4 – 22.8), and 63.2 months, respectively. There was a significant difference between H-R, I-R, and L-R (log-rank test; p =.000, Figure 1). Moreover, among the patients with DLBCL, the median OS time of H-R, I-R, and L-R were 4.3 months (95% CI, 0.9 – 7.8), 18.8 months (95% CI, 2.2 – 35.3), and not reached, respectively. There was a significant difference among H-R, I-R, and L-R for patients with DLBCL (log-rank test; p =.001, Figure 2). Among I-R patients in all lymphomas, the OS was significantly longer in the ICE arm than in the DHAP arm (18.8 months vs 13.6 months, respectively; p =.030). Moreover, the OS in I-R patients with DLBCL was longer in the ICE arm than in the DHAP arm significantly (not reached vs 13.6 months, respectively; p =.024). There was no significant difference between the ICE and the DHAP arms with H-R and L-R in both all lymphomas and DLBCL. Conclusion Elevated CRP level, elevated LDH level, and anemia were predictive factors for poorer outcome among patients with recurrent or refractory malignant lymphoma treated with ICE or DHAP. We classified patients into three groups based on these three predictors, and there was a significant difference in OS among H-R, I-R, and L-R in patients with both all lymphomas and DLBCL. ICE predicted better outcome than DHAP in I-R with both all lymphomas and DLBCL. Disclosures: Mishima: Chugai Pharmaceutical Co, Ltd: Consultancy. Yokoyama:Chugai Pharmaceutical Co, Ltd: Consultancy. Hatake:Chugai pharmaceutical co, ltd: Honoraria, Research Funding; Kyowa Hakko Kirin Co, Ltd: Honoraria, Research Funding; Takeda Pharmaceutical Co, Ltd: Honoraria, Research Funding; Pfizer japan Inc: Research Funding; Ono Pharmaceutical Co, Ltd: Honoraria.

Abstract 2678 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a wide range of clinical outcomes. Rituximab added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, R-CHOP has made a marked improvement in outcome in patients with DLBCL. The International Prognostic Index (IPI), which consists of age > 60 years, stage III/IV, elevated lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) performance status (PS) † 2, and more than one extranodal (EN) site of disease, remains the most commonly used system for risk classification in DLBCL. However, recent studies suggested that new agent has altered the significance of previously recognized risk factors. Here we investigate the prognostic impact of reported risk factors in a large DLBCL patient cohort in a single institute to determine a better prognostic model in rituximab era. Patients and Methods: In total, 250 newly diagnosed DLBCL patients treated with R-CHOP regimen at the Cancer Institute Hospital of JFCR between October 2003 and December 2008 were included and analyzed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared among risk groups using the log rank test. The Cox proportional hazards model was used to test the significance of prognostic factors. ROC curve was used to determine optimal serum level of sIL-2R and LDH as a cut off value for 4-year mortality risk. Results: The median age of patients was 65 years (range 23–88 years), 56% were male. The median follow-up time was 49 months (range 1–90 months) and 39 deaths had been recorded by the time of the last follow-up. The IPI still remains predictive with an OS ranging from 52.4% to 91.6% at 4 years; however it cannot discriminate between low and low-intermediate group. Revised IPI was valid as well with an OS ranging from 63.3% to 97%. In univariate analysis, elevated sIL-2R level, B symptom, elevated LDH level, PS>2, age>65, stage III/IV, CD5 positive, and EN>1 were significant as poor prognostic factors whereas sex, bulky mass, MIB1 index >90%, Non-GCB were not. Furthermore, multivariate analysis showed that only sIL-2R>924U/ml, CD5 expression, and EN>1 were significant with relative hazard 1.4∼17.5, 1.4∼8.9, and 1.3∼4.7, respectively. As elevated sIL-2R was the most powerful prognostic factor, we performed further analysis on this parameter. Average serum sIL-2R level was 2,775U/ml (range from 220U/ml to 43,100U/ml) with a normal limit of upper is 230U/ml. ROC curve demonstrated that serum sIL-2R was more optimal value than serum LDH to identify high risk patients for 4-year mortality after initiation of R-CHOP therapy and cutoff value of sIL-2R was 924U/ml (1.73 upper limit of normal). sIL-2R level can be divided into three distinctprognostic groups. Patients with sIL-2R=4,625U/ml fall into a poor group with a 4-year OS:59.6% and 4-year PFS:54.7% (P < 0.001). Conclusions: sIL-2R level is an independent and powerful prognostic factor in serum level dependent manner in DLBCL patients treated with R-CHOP. This prognostic model should be reassessed on a larger scale and prospective study. Disclosures: No relevant conflicts of interest to declare.

Abstract 1760 Background Other than MALT, gastric diffuse large B cell lymphoma is a very common disease in malignant lymphoma. However the treatment strategy is controversial. Although a high efficacy of rituximab plus CHOP (RCHOP) has been proven in diffuse large B cell lymphoma (DLBCL), the decision to operate is still usual among surgeons in limited stage of gastric DLBCL. Koch et al. described that CHOP14 with radiotherapy is very effective for aggressive gastric lymphoma without surgery. In this report, though, the histology was various and mixed with MALT and DLBCL. Studies about only gastric DLBCL were very few, but, in some small size studies about RCHOP to gastric DLBCL, a good prognosis has been shown. If chemotherapy with radiotherapy alone gave rise to a complete response to gastric lymphoma, the patients could avoid gastric resection. Therefore it is necessary to devise a strategy for gastric DLBCL treatment. Patients and Methods We retrospectively analyzed the patients who diagnosed with gastric DLBCL between November 2003 and October 2008. The cases with limited stage were treated with 3 cycles of RCHOP with radiotherapy and the cases with advanced stage were treated with 6 cycles of RCHOP without radiation. All cases were evaluated with PET/CT after treatment. Statistical analysis of progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimators. Comparison between categories was performed by means of log-rank test. We estimated age-adjusted IPI, GC or non GC subtype, and hemoglobin level (Hb Result Total 40 cases were analyzed in this study. Median age was 65.5 years old and males were 21 (52.5%). For age-adjusted IPI, low was 22, low-intermediate was 9, high intermediate was 3, and high was 6. 15 cases (27.5%) were limited stage and they all received 3 cycles of RCHOP with radiation. 25 cases (72.5%) were stage II or more, and they all were treated with 6 cycles of RCHOP. GC and non-GC types were 30 (75%) and 10 (25%), respectively. The average of observation duration was 1274 days. Four cases dropped out from these regimens because of adverse event. CR rate was 92.8% (37/40) and one case progressed and one case relapsed. Two year-OS and PFS rate were 95.2% and 91.8%, respectively. Main adverse events were grade 4 neutropenia47.5% and febrile neutropenia 17.5%. There was no case with gastric bleeding after chemotherapy. There was one case of SIADH induced by vincristine, one case of grade 3 of hepatotoxity, confusion, and one case of intestinal pneumonia, respectively. Secondary gastric cancer after radiotherapy did not occur. We performed univariate statistical analysis about aa-IPI, GC or non GC subtype, and Hb level, then, there was tendency of poor prognosis only in high risk of aa-IPI (p=0.0512). However there was no significant difference in multivariate analysis. Discussion RCHOP with or without radiation therapy was a very effective regimen and well-tolerated for gastric DLBCL patients. The result of our study, which was a small sample size, showed a better result than previous reports about DLBCL with RCHOP. Although the cases with severe bleeding or deep ulcer were included in this study, bleeding stopped and severe ulcers improved after chemotherapy in all such cases, so surgical treatment was not necessary. There was no report about direct comparison of the therapy with or without surgical treatment in gastric DLBCL, although RCHOP with radiation could preserve the organ and keep quality of life after treatment. We should recommend RCHOP with or without radiation for gastric DLBCL as the first line treatment. Disclosures: No relevant conflicts of interest to declare.

Abstract 2815 Backgrounds: Next to diffuse large B-cell lymphoma and follicular lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the third most common subtype of non-Hodgkin's lymphomas. Their clinical course usually is indolent with long-progression free survival (PFS) and overall survival (OS). Because it can involve many sites throughout the body, a patient of MALT lymphoma is often treated by different strategies, radiation therapy, surgery, or chemotherapy. The aims of study are to assess the clinical characteristics and treatment results of this one of the most common lymphoma and to analyze the prognostic factors. Patients and Methods: Ninety-eight patients with MALT lymphoma consecutively diagnosed by an expert hematopathologist from March 2001 to October 2008 were reviewed retrospectively. They all underwent standarlized staging program in our hospital. Majority of the patients had localized disease. Comparisons were performed between patients with gastric and non-gastric MALT lymphoma. Prognostic significance of various factors for PFS was examined. Statistical analyses of PFS and OS were calculated using Kaplan-Meier estimators. Comparison among categories was performed by means of log-rank test. Using Cox proportional hazards regression analysis, multivariate analysis was performed about estimated risk factors. Results: Patients were 48 males and 50 females. Median age was 62 years old (range 26 to 85 years old). Only 17 patients had advanced diseases. 52 had the primary site located in the stomach, and 22 had in the orbit, and 8 had in the salivary grand. Ninety-three patients received some treatment, including radiation, chemotherapy and surgery. Mainly, localized gastric lymphoma and non-gastric lymphoma were performed eradication of Helicobacter Pylori and the radiation therapy respectively. All but two patients with disseminated diseases treated with rituximab-combined chemotherapy. The response rate of the initial treatment was 94%, and the CR rate was 76%. After a median follow-up time of 40 months (range 1 to 109 months), 3-years OS and PFS were 100% and 89%, respectively. 3-year PFS for localized disease and advanced disease were 94% and 73%, respectively. 3-years PFS was 95% for gastric MALT lymphoma and 82% for non-gastric lymphoma. All of the patients with localized gastric MALT lymphoma were progression-free at three years after the treatment. Adverse prognostic factors for PFS were non-gastric lymphoma and disseminated disease. In a multivariate analysis, shorter PFS was associated with non-gastric lymphoma. Discussion: Our analysis indicates that MALT lymphoma is an indolent disease with long survival, but patients with non-gastric lymphoma and advanced diseases were prone to have worse prognosis. H.pilori eradication was an effective first-line treatment for the localized gastric MALT lymphoma and leads to a favorable long term out-come. Rituximab-combined chemotherapy was effective even though for advanced disease. In this rituximab era, clinical course of this indolent lymphoma may become much better. However, the therapeutic strategy of MALT lymphoma is still controversial. We need to assess and clear up which is the best. Disclosures: No relevant conflicts of interest to declare.

Abstract 2814 Background: Central nervous system (CNS) relapse is considered an infrequent but severe, nearly fatal complication of diffuse large B-cell lymphoma (DLBCL) following initial chemotherapy. Intrathecal (IT) prophylaxis cannot be recommended for all DLBCL patients because of the low probability of CNS relapse. Rituximab (R) added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been reported as likely to reduce the frequency of CNS relapse in patients with DLBCL, however, the efficacy of rituximab on the prognosis of CNS relapse compared with those who relapsed at other sites and predictive factors for CNS relapse in patients treated with rituximab contained chemotherapy remain unclear. The main objective was to determine the high-risk patients who need IT prophylaxis and the outcomes of CNS relapse compared with relapse on other sites. Patients and Methods: Diffuse large B cell lymphoma patients treated with rituximab contained CHOP regimen with or without radiotherapy and IT prophylaxis at Cancer Institute Hospital of JFCR between October 2003 and December 2006 were analyzed retrospectively. CNS relapse was defined as leptomeningeal, brain parenchymal, or intradural involvement with lymphoma, based on radiological findings or the presence of malignant lymphoma cells in spinal fluid. Results: A total number of 137 patients were identified. IT prophylaxis was administered in 13 of 137 patients (9.48%) depending on the sites of lymphoma involvement, such as bone marrow involvement, testis, paranasal sinuses. 17 of 137 patients (12.4%) underwent radiotherapy after chemotherapy because of early stage or their residual disease. With a median follow-up period of 4.4 years, 9 patients had experienced CNS relapse (6.7%: 3.0–12.1, 95%CI) among 30 documented relapses, with 9 presenting with nodal relapse alone and 21 presenting with extranodal relapse including CNS. IT prophylaxis and the addition of radiotherapy did not affect the frequency of CNS relapse (P=0.6 and 0.26). Median time to CNS relapse was 20 months. Overall survival (OS) was significantly inferior in CNS relapse patients to other-sites relapse patients, (median OS, 61 months vs. did not occur; P =.042). Nevertheless, OS was not significantly different between patients with CNS relapse or at other sites. In univariate analysis, factors associated with CNS relapse (P < 0.05) included age over 65 years and serum levels of soluble IL-2 receptors (sIL-2R) ≧10 ULN (upper limit of normal) but not sex, PS ≧3, stage ≧4, B symptom, bulky mass, elevated LDH >2 ULN, elevated MIB1 index ≧90%, poor revised-international prognostic index (R-IPI), extranodal sites ≧2, or type of GC or non-GC. Multivariate Cox regression analysis identified increased serum levels of (sIL-2R) (P =0.037) as an independent predictive factor for CNS relapse (P=0.04, HR=7.02: 95%CI=1.87-26.22). Five of 9 CNS relapse patients were still alive with the combination treatment of whole brain irradiation, systemic chemotherapy (R- dexamethasone, cisplatin, cytarabine) and intrathecal chemotherapy. Conclusions: The incidence rate of CNS relapse in 137 DLBCL patients treated with R-CHOP, CEOP regimens may be lower than with CHOP in agreement with previous studies. Furthermore, rituximab may improve OS after CNS relapse. Ten times increased serum s-IL2R is a potential independent risk factor for CNS relapse and should be included in the IT prophylaxis indication in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

Abstract 4763 INTRODUCTION Peripheral blood involvement (leukemic presentation) is considered as a part of bone marrow involvement and detected about 18% of bone marrow (BM) involvement of follicular lymphoma (FL). It is not known whether leukemic presentation is an adverse prognostic factor in rituximab era. METHOD We retrospectively evaluate prognostic value of peripheral blood involvement in patients with follicular lymphoma received rituximab containing regimen as an initial therapy from October 2000 to January 2009. Leukemic presentation was defined by morphologic identification of an abnormal lymphoid population in the peripheral blood. RESULT Total 129 patients were treated with rituximab containing initial therapy. Bone marrow involvement was detected in 39 /108 (36.1%) patients and leukemic presentation was identified in 8 / 39 (20.5%) of patients with BM involvement. Leukemic presentation shows significant poorer progression free survival than BM involvement without peripheral blood involvement. (2yr PFS 23.4% vs 73.3% p=0.015) Multivariate analysis conducted by Cox proportional hazard analysis including five variables of FLIPI revealed Hb CONCLUSION Leukemic presentation is a significant adverse prognostic factor of FL in rituximab era. Prognostic value of leukemic presentation should be validated in further study. Disclosures: No relevant conflicts of interest to declare.