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Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Palliative chemotherapy can be considered in patients with metastatic disease. Although mitotane- or cisplatin-based chemotherapy regimens are widely used, the effects of these agents have been limited. We have experienced a case that showed a partial response with sunitinib after failure of mitotane-based cytotoxic chemotherapy. The clinical benefit from sunitinib persisted 7.5 months in this case. To our knowledge, this is the first reported case showing the effects of sunitinib on metastatic ACC.

Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the proapoptotic potency of piceatannol, the molecular mechanisms underlying the anti-leukemic activity have not yet been studied in detail. This study examined the effects of piceatannol on the growth of the human leukemia cell line U937. The results showed that piceatannol inhibits the viability of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, DNA fragmentation and the accumulation of the sub-G1 phase. RT-PCR and immunoblotting data showed that treating the cells with piceatannol caused the down-regulation of anti-apoptotic Bcl-2 and cIAP-2 expression. Piceatannol-induced apoptosis was also associated with the proteolytic activation of caspase-3, and the degradation/cleavage of poly (ADP-ribose) polymerase protein. z-DEVD-fmk, a caspase-3-specific inhibitor, blocked the activation of caspase-3 and increased the survival of the piceatannol-treated U937 cells, suggesting that caspase-3 activation is essential for piceatannol-induced apoptosis.

The aim of this study was to develop a new fermentation method in order to improve the digestion of soybean protein, and to promote normal fermentation of soybean. A proximate composition, such as moisture, pH, and reducing sugar, of fermented soybeans by the new fermentation was similar to those of controls. Neutral protease activity, the most important factor for fermented soybean products, was the highest, having about 636 U/g at 54 h fermentation. The content of total free amino acid was almost 3-18 times higher than controls. The three-step fermented soybeans can be used as a functional food ingredient for human consumption, with higher protein digestibility.

Background: Given the increasing incidence of multiple myeloma (MM) in Asian countries, effective treatment options for these patient (pt) populations are needed (Kim et al, Am J Hematol, 2014). The pivotal phase 3 FIRST trial investigated continuous treatment with lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) in pts with newly diagnosed MM (NDMM) who were ineligible for transplant from 18 countries, including China, South Korea, and Taiwan. Treatment with Rd continuous in the FIRST trial improved progression-free survival (PFS; hazard ratio [HR] = 0.72; P < .001) and overall survival (OS; HR = 0.78; P = .02) compared with melphalan-prednisone-thalidomide (MPT; Benboubker et al, N Engl J Med, 2014). This subanalysis of the FIRST trial examined the efficacy and safety of Rd continuous in the Asian population. Methods: Pts with NDMM aged ≥ 65 years or ineligible for transplant were randomized to 3 treatment arms: Rd continuous, Rd for 18 cycles (Rd18; 72 weeks), or MPT for 12 cycles (72 weeks). The primary endpoint was PFS in pts treated with Rd continuous vs MPT (primary comparators). Secondary endpoints included OS, overall response rate (ORR), duration of response (DOR), and safety. Data cutoff was May 24, 2013; response and progression were assessed by an independent response adjudication committee. OS was assessed with extended follow-up at a data cutoff of March 3, 2014. Results: Of the 114 pts enrolled in China, South Korea, and Taiwan, the median age (68 yrs [range, 43-86 yrs]) was similar across the Rd continuous (n = 36), Rd18 (n = 38), and MPT (n = 40) arms but was lower than that of the overall study population (73 yrs [range, 40-92 yrs]). Compared with the overall population, pts in Asia also had a higher rate of International Staging System stage III disease (45% in Asia vs 41% overall), a higher rate of Eastern Cooperative Oncology Group performance status ≥ 2 (28% in Asia vs 22% overall), and double the rate of severe renal insufficiency (creatinine clearance < 30 mL/min; 18% in Asia vs 9% overall), the latter of which was more frequent in the MPT (23%) and Rd18 (24%) arms vs the Rd continuous (8%) arm. There were more male than female pts (58% vs 42%) in the Asian population, with the exception of the MPT arm (50% each). The median treatment duration was 18.4 mos (range, 0.5-35.9 mos) for Rd continuous, 11.0 mos (range, 0.6-19.6 mos) for Rd18, and 11.1 mos (range, 0.3-19.1 mos) for MPT. Treatment with Rd continuous vs MPT resulted in a 39% reduction in the risk of progression or death (hazard ratio [HR] = 0.61; 95% CI, 0.33-1.14; Table). Rates of 2-year PFS were nearly doubled with Rd continuous (48%) vs MPT (25%). Rd continuous also resulted in a 48% reduced risk of death vs MPT (HR = 0.52; 95% CI, 0.24-1.13). Rates of 3-year OS were greater with Rd continuous (70%) vs MPT (56%). Similar improvements were observed for PFS and OS with Rd continuous vs Rd18. ORR was greater in the Rd continuous (78%) arm vs the Rd18 (66%) and MPT (58%) arms. Median DOR was not reached for Rd continuous and was 17.2 and 13.8 mos for Rd18 and MPT, respectively. The most frequent grade 3/4 adverse events with Rd continuous, Rd18, and MPT treatment were neutropenia (25%, 34%, 44%), anemia (19%, 5%, 15%), pneumonia (6%, 24%, 15%), and thrombocytopenia (14%, 5%, 5%). Deep vein thrombosis was reported in only 1 pt on the MPT arm, and pulmonary embolism was reported in 1 pt on each treatment arm. There were no reports of second primary malignancies in the Asian population. Conclusions: Rd continuous treatment was associated with numerically larger PFS and OS benefits and higher response rates compared with MPT in the Asian subgroup of the FIRST trial, although pt numbers were small. Results from the Asian subgroup were consistent with that of the global population, with no unexpected safety signals observed, a low rate of thromboembolic events, and no second primary malignancies as of the data cutoff. These findings support the use of Rd continuous as standard treatment for pts with NDMM who are ineligible for stem cell transplant, including in Asian populations. Disclosures Qiu: Celgene Corporation: Speakers Bureau; Johnson & Johnson: Speakers Bureau; Roche: Speakers Bureau. Yiu:Celgene Corporation: Employment, Equity Ownership. Chen:Celgene Corporation: Employment, Equity Ownership. Ervin Haynes:Celgene Corporation: Employment, Equity Ownership. Hulin:Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees.

Purpose: This study was aimed to investigate the relationship between the allergen components and moderate-to-severe allergic reactions in patients with buckwheat allergy. Methods: Fifteen patients with a history of buckwheat ingestion and a buckwheat specific IgE level ≥0.35 kU/L were enrolled. They were divided into 2 groups according to clinical severity scores, with 0–1 being asymptomatic-to-mild and 2–4 being moderateto-severe symptoms. Immunoblotting was performed to investigate IgE reactivity toward buckwheat allergens and to measure intensity of each component by using a reflective densitometer. Results: The proportions of positive band to the 16 kDa (62.5% vs 0%, P=0.026) and 40–50 kDa (87.5% vs 28.6%, P=0.041) buckwheat allergens in the grade 2-4 group were higher than those in grade 0-1 group. The level of buckwheat specific IgE of grade 2-4 group was higher than that of grade 0-1 group (41.3 kU/L vs 5.5 kU/L, P=0.037). The median optical densities (ODs) of IgE antibody binding to 40-50 kDa protein were higher in the grade 2-4 group, compared with those in the grade 0-1 group (130% OD vs 60.8% OD, P=0.037). Conclusions: The 40–50 kDa protein is implicated as an important allergen to predict moderate-to-severe clinical symptoms in Korean children with buckwheat allergy.

36 This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MISP) (NRF20090078392, BAERI). Received 25 February 2015, Revised 5 March 2015, Accepted 8 March 2015 Correspondence: Dong Joon Lee (djlee@paik.ac.kr) Tel: 82-31-910-7730, Fax: 82-31-915-0885 cc This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Calculation of Dose Distribution for SBRT Patient Using Geant4 Simulation Code

목적: 만성골수성백혈병의 진단 및 치료를 위한 한국 치료 가이드라인은 한국 실정에 맞춘 내용을 통해 국내 치료방침 및 연구 기준을 표준화하기 위하여 제정되었다. 방법: 국내 만성골수성백혈병 전문가들을 대상으로 한 설문 조사와 자문 미팅을 거쳐 본 가이드라인을 작성하였다. 결과: 본 가이드라인에는 만성골수성백혈병의 진단 및 초기 검사, 예후인자, 만성기에서의 초치료 및 치료 중 확인 사항과 반응 평가, 이차 약제 변경 및 이후의 치료 반응 평가, 가속기 및 급성기에서의 치료와 반응 평가, 동종 조혈모세포이식, 독성 평가 및 관리 등 만성골수성백혈병의 전반에 대한 국내 전문가들의 의견을 종합한 권고안을 제시하고 있다. 결론: 만성골수성백혈병의 치료는 최근 많은 발전이 있었으며 향후 예후 평가에 대한 연구 및 약제의 중단 가능성 평가 연구 등 다양한 연구들을 통해 더욱 더 많은 향상이 있을 것으로 기대된다.

Background Few clinical studies have clarified the prognostic factors that affect clinical outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after immunochemotherapy. Methods A total of 158 patients with relapsed or refractory DLBCL were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) before and after salvage therapy. All enrolled patients previously received the ifosfamide, carboplatin, and etoposide regimen. Clinical outcomes were compared according to several factors (age ≥ 65 years, low age-adjusted International Prognostic Index [aa-IPI], maximum standardized uptake value [SUVmax]

Food-dependent exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening clinical reaction in which anaphylaxis develops when physical activity occurs within a few hours after ingesting a specific food. An 18-year-old girl experienced generalized urticaria, periorbital swelling, and dyspnea repeatedly by exercise after intake of a red ginseng health supplement. A confirmed diagnosis was established in this case by using an exercise challenge test after ingesting mixed-plant extract containing red ginseng health supplement. To the best of our knowledge, this is the first case of FDEIA caused by components in a red ginseng health supplement. (Allergy Asthma Respir Dis 2015;3:219-223)

Water extract (WE) of Cordyceps militaris has been reported to produce antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not been known. In this study, we investigated whether water extract of C. militaris induces the phenotypic and functional maturation of dendritic cells (DC). It profoundly increased CD40, CD54, CD80, CD86, and MHC class II expression in murine bone marrow (BM)-derived myeloid DC. Endocytosis was assessed by the uptake of FITC-dextran and FITC-albumin. The ability of unstimulated DC (UT-DC) to uptake dextran and albumin was higher than that of WE- or LPS-stimulated DC (LPS-DC). Also, UT-DC secreted a low concentration of IL-12, while WE- or LPS-DC secreted higher levels of IL-12 than UT-DC. WE not only formed morphologically mature DC and clusters, but also induced predominantly functional maturation. Moreover, WE is shown to promote the cytotoxicity of specific-cytotoxic T lymphocyte (CTL) induced by DC which were pulsed with P815 tumor-lysate during the stage of antigen presentation. These results suggest that DC maturation by WE can play a critical role in the improvement of the immunoregulatory function in patients with impaired host defense.

Backgroud: Substantial number of acute myeloid leukemia(AML) patients does not respond to induction chemotherapy (refractory) or relapse after achieving complete remission (CR) with standard induction chemotherapy. In relapsed/refractory AML, therapeutic options are still undefined and unsatisfactory. By the way, new regimen integrating cladribine yields promising outcomes in recent studies. We intended to reveal the efficacy of CLAG/CLAGM and to find out predictive markers for outcome in relapsed/refractory AML patients. Methods: Relapsed/refractory AML patients who were treated with CLAG or CLAGM between 2004.5 - 2014.7 in two institutions (Seoul National University Hospital/Seoul National University Bundang Hospital) were retrospectively reviewed. The regime CLAG consists of cladribine 5mg/m2 on days 1-5, cytarabine 2gm/m2 on days 1-5 and filgrastim 5 mcg/kg on days 0-5. The regimen CLAGM includes addition of mitoxantrone 10mg/m2 to CLAG regimen on days 1-3. We analyzed factors affecting complete remission(CR), relapse free survival(RFS) and overall survival(OS). Results: The total of 56 patients (Male:Female = 36:20, median age 51 years) were analyzed. Overall CR rate was 50%, CR rate was 44% for CLAG, 55% for CLAGM respectively, and was not significantly different between the two regimens (p=0.511). Poor predictive markers for CR rates after CLAG/CLAGM included secondary AML (p=0.006), and poor cytogenetic risk group based on MRC criteria (p The median OS who received CLAG/CLAGM was 13.5 months (95% CI; 10.2 – 16.7 months); 13.2 months (95% CI ; 8.9 – 17.5 months) for CLAG and 13.5 months (95% CI ; 10.4 – 16.6 months) for CLAGM, no statistical difference (p=0.899). Poor prognostic factor for OS included secondary AML (p Conclusion: CLAG/CLAGM is an efficacious regimen for refractory/relapsed AML as previously reported. Especially whether the patients achieved CR before CLAG/CLAGM is favorable prognostic factor. However, only limited benefit is shown in secondary AML patients and poor cytogenetic risk group patients. Allogeneic ASCT as consolidation therapy is definitely necessary to improve outcome. Disclosures No relevant conflicts of interest to declare.

Pancreatic cancer is a highly lethal disease. Although gemcitabine is activelyused in pancreatic cancer, modest activity and relativeresistanceare revealed.P21-activated kinases(PAKs) are involved in cytoskeletal reorganization, gene transcription, cellproliferation and survival, and oncogenic transformation.The gene amplification and protein overexpression of PAK1 and PAK4were reported in pancreatic cancer, which were associated with K-ras mutation, MUC13 and Smad4. Therefore, we hypothesized that PAKs could predict the drug-sensitivity of gemcitabine in pancreatic cancer and could be a therapeutic target. Using cell viability assay of human pancreatic cancer cell lines (Capan1, Capan2, MIA-paca2, PANC1, Aspc1, SNU213, SNU410) for gemcitabine, Capan-2, PANC-1 and SNU-410 cell lines was identifiedas resistant cell lines for gemcitabine. Through western blots of molecules related with down-steam pathway and drug-sensitivity, higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1) were associated with the resistance for gemcitabine. PAK4 down-regulation through siRNA induced the up-regulation of hENT1, which is well-known as predictive marker for gemcitabine activity. In resistance cell lines (Capan-2, PANC-1, SNU-410), down-regulation of PAK4 through siRNArestored the drug-sensitivity for gemcitabine. In conclusion, PAK4 can be a potential predictive marker and therapeutic target in gemcitabine chemotherapy for pancreatic cancer. Citation Format: Sung Ung Moon, Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Hyun Chang, Jeong Ok Lee, Yu Jung Kim, Keun Wook Lee, Jee Hyun Kim, Soo Mee Bang, Jong Seok Lee. P21-activated kinase 4 (PAK4) as a predictive marker for gemcitabine in pancreatic cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 912. doi:10.1158/1538-7445.AM2014-912

BACKGROUND/OBJECTIVES: Due to its beneficial health effects, use of buckwheat has shown a continuous increase, and concerns regarding the allergic property of buckwheat have also increased. This study was conducted for evaluation of the hydrolytic effects of seven commercial proteases on buckwheat allergens and its allergenicity. MATERIALS/METHODS: Extracted buckwheat protein was hydrolyzed by seven proteolytic enzymes at individual optimum temperature and pH for four hours. Analysis was then performed using SDS-PAGE, immunoblotting, and competitive inhibition ELISA (ciELISA) with rabbit antiserum to buckwheat protein, and direct ELISA with pooled serum of 21 buckwheat-sensitive patients. RESULTS: Alkaline protease, classified as serine peptidase, was most effective in reducing allergenicity of buckwheat protein. It caused decomposition of the whole buckwheat protein, as shown on SDS-PAGE, and results of immunoblotting showed that the rabbit antiserum to buckwheat protein no longer recognized it as an antigen. Allergenicity showed a decrease of more than 50% when pooled serum of patients was used in ELISA. Two proteolytic enzymes from Aspergillus sp. could not hydrolyze buckwheat allergens effectively, and the allergenicity even appeared to increase. CONCLUSIONS: Serine-type peptidases appeared to show a relatively effective reduction of buckwheat allergenicity. However, the antigenicity measured using rabbit antiserum did not correspond to the allergenicity measured using sera from human patients. Production of less allergenic buckwheat protein may be possible using enzymatic hydrolysis.

Background VMP regimen for newly diagnosed myeloma patients is well-documented treatment. However patients in real practice generally have worse performance status and less attention than those in clinical trials. Thus we conducted observational study to evaluate the efficacy and toxicity of VMP treatment in newly diagnosed Korean myeloma patients. Patients and Methods Data were prospectively collected from 39 hospitals. One hundred seventy three patients who started VMP as first line from 2011 May to 2012 April were included for analysis. Results Median age was 71 and 22.5% were more than 75 years old. Fifty-seven per cent were male sex. IgG type was most common (61.9%) and IgA 24.9%. ISS stage I was 13.8% and III was 51.5%. Patients with high risk FISH (Del17p, t(4;14), and t(4;16)) were 4.1%, 4.1%, and 2.3% respectively. Dose and schedule was followed original VISTA trial except for use of prednisolone instead of prednisone. Median 5cycles (range 1-9) were given and 105 patients stopped in the course of treatment. Most common cause were adverse event (28.8%) followed by disease progression or no response (19.6%). Twenty-five mortality cases were reported and 22 were in the course of treatment. The most common cause of mortality was infection (61%) followed by disease progression (13%). Overall response rate was 72.3% and response more than VGPR was 37.6%. Median progression free survival is 455 days and median OS was 504 days. One year PFS was 80.9 % and one year OS was 83.4%. Most common toxicity was cytopenia, peripheral neuropathy, and gastrointestinal toxicities such as nausea and diarrhea. Peripheral neuropathy of all grade and grade 3 or more was 58.6% and 6.36%, respectively Discussions Even though patients with higher proportion of ISS stage, efficacy of VMP regimen was considerable in Korean patients. With relatively high mortality due to infection in the course of treatment prophylactic measures for infection need to be developed. To reduce the incidence of peripheral neuropathy, close observation and intervention are needed to prevent aggravation of neuropathy. Disclosures: Off Label Use: lenalidomide in newly diagnosed myeloma. Kwak:celgene: Research Funding.

e15129 Background: Several Western guidelines recommend the routine use of pharmacologic thromboprophylaxis for cancer surgery patients to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic perioperative thromboprophylaxis in Asian gastric cancer (GC) patients has not been clearly determined. Methods: To determine the necessity of routine perioperative pharmacologic thromboprophylaxis in Korean gastric cancer patients, the incidence of postoperative VTE was prospectively evaluated in gastric cancer patients receiving surgery. Among 610 GC patients who had received surgery, 375 patents prospectively underwent routine duplex Doppler ultrasonography (DUS) on days 5-12 following surgery to detect VTE and then VTE-related symptoms and signs were checked at 4 weeks after surgery (cohort A). The 235 patients that declined DUS were registered to cohort B and the occurrence of postoperative VTE was retrospectively analyzed. Results: In cohort A, symptomatic or asymptomatic VTE until 4 weeks after surgery was detected in 9 patients [2.4%; 95% confidence interval (CI); 0.9-3.9]. Tumor stage was a significant factor related to VTE development [stage I, 1.4%; stage II/III, 2.4%; stage IV, 9.7% (P = 0.008)]. In multivariate analysis, patients with stage IV had a higher postoperative VTE development [odds ratio, 8.18 (95% CI, 1.54-43.42)] than those with stage I. In cohort B, a low incidence of postoperative VTE was reaffirmed; only one postoperative VTE case (0.4%) was observed. Conclusions: The incidence of postoperative VTE in Korean GC patients was only 2.4%. Risk-stratified applications of perioperative pharmacologic thromboprophylaxis are thought to be more appropriate than the routine pharmacologic thromboprophylaxis in Korean GC patients receiving surgery.

TO THE EDITOR: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy. Risk factors for HIT include the type of heparin used, duration of heparin exposure, and clinical setting. Here, we report a 76-year-old man who presented with life-threatening pulmonary thromboembolism and deep-vein thrombosis, preceded by a dramatic decrease in platelet count 1 week after radical cystectomy for transitional cell bladder carcinoma. He was diagnosed with type II HIT caused by a small amount of unfractionated heparin mixed into his total parenteral nutrition (TPN) solution. One thousand units heparin per day were added to his TPN for 1 week. A heparin-platelet factor-4 antibody enzyme-linked immunosorbent assay of his serum was strongly positive. After cessation of TPN infusion, argatroban was started for thrombosis. His platelet count gradually increased to a normal level, and the thrombosis was treated successfully. This case suggests HIT should be suspected in patients with typical clinical manifestations and risk factors, even if the infused heparin dose is small. Heparin is widely used in a variety of medical therapies from the treatment of life-threatening acute thromboembolisms to the maintenance of indwelling vascular catheter patency. However, heparin therapy is often complicated by thrombocytopenia. The incidence of heparin-induced thrombocytopenia (HIT) in patients who receive heparin including unfractionated heparin and low-molecular-weight heparin is 0.1-5% [1]. There are 2 types of HIT. Type I HIT is a relatively common non-immune reaction that causes an asymptomatic, transient, and mild decrease in platelet count. In contrast, type II HIT is an immune complex disorder involving heparin bound to the platelet-specific chemokine, platelet factor-4 (PF4). These heparin-PF4 complexes activate both platelets and endothelial cells, resulting in platelet consumption and endothelial injury with thrombosis and disseminated intravascular coagulation [2]. Heparin use could go unnoticed if it is not applied as a conventional anticoagulant but rather as a supportive agent to maintain vasc,ular patency. However, unrecognized HIT can lead to life-threatening complications. Therefore, it is important to suspect HIT in patients who develop acute thrombosis or thrombotic tendency preceded by a decrease in platelet count during or soon after heparin therapy, even if the infused amount is small. Immediate discontinuation of heparin administration and initiating alternative anticoagulant therapy are critical for avoiding further thrombosis, even before laboratory results are available [3]. To the best of our knowledge, this is the first report on a patient who experienced type II HIT after low-dose heparin added to his total parenteral nutrition (TPN) for 1 week.

Abstract 1691 Dasatinib and nilotinib have been founded to be effective and well-tolerated in patients who develop resistance or intolerance to imatinib. Not enough data are currently available to recommend one over the other as the preferred second-line therapy based on efficacy data. Therefore we planned a multicenter retrospective study to analyze the efficacy and safety of dasatinib and nilotinib in patients with imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase. In this Korean multicenter study, 126 patients imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase were treated with dasatinib (n=76) or nilotinib (n=50) The purpose of this study was to compare rates of cytogenetic and molecular response rate, event-free survival (EFS), progression-free survival (PFS) and overall survival (OS), and toxicities of nilotinib and dasatinib treatment of imatinib-resistant or –intolerant chronic myeloid leukemia in chronic phase. PFS was defined as the time from the start of treatment to the earliest date of any of following event: loss of complete hematologic response (CHR), loss of major cytogenetic response (MCyR), progression to accelerated phase (AP) or blastic phase (BP), discontinuation due to treatment failure as assessed by the clinician, and death from any cause on therapy. Event was defined by any one of the following: loss of CHR, loss of MCyR, progression to AP or BP, discontinuation due to treatment failure as assessed by the clinician, treatment discontinuation due to toxicity, and death from any cause on therapy. For dasatinib and nilotinib group, median ages (51 years old vs. 53), median durations of CML (23.7 months vs. 19.8 ) before receiving dasatinib or nilotinib and duration of prior imatinib treatment (21.7 months vs 17.7) were comparable. Nilotinib group had a higher proportion of intermediate and high sokal scores at the time of diagnosis than dasatinib group (41.5 vs 29.3% (high), 41.5% vs 32.5%(intermediate), 17.1% vs 37.9(low), p= 0.04). After median follow-up durations of 20.2 months of dasatinib group and 25.3 months of nilotinib group, the rates of major molecular response were 50.0% for dasatinib group and 59.6% for nilotinib group (p=NS) and the rates of MCyR (complete and partial cytogenetic response) were 78.4% for dasatinib group and 74.5% for nilotinib group (p=NS). The estimated EFS at 24 months was 67% and 48% in dasatinib and nilotinib group, respectively. (p Disclosures: No relevant conflicts of interest to declare.

Abstract 2247 Introduction Patients (pts) with cancer have been associated with increased risk of recurrent venous thromboembolism (VTE). However, few data are available regarding the recurrent VTE in Asian pts with advanced solid cancers. Thus, the aim of the study is to investigate the incidence and risk factors for recurrent VTE in pts with advanced solid cancers receiving anticoagulation therapy after index VTE. And, we also evaluate the prognostic impact of recurrent VTE on overall survival (OS) in this population. Methods This study was conducted using data from the web-based registry of the Korean Thrombosis Working Party (http://kdvt.chamc.co.kr), which is an ongoing, multicenter database for recruiting consecutive pts presenting with VTE. Pts were included in the study cohort if they had been diagnosed with recurrent/metastatic solid cancers between May 2004 and Dec 2011 and initiated anticoagulation therapy. Pts were excluded if they had received a diagnosis of hematologic malignancies, if solid cancers were not recurrent or metastatic disease, if index VTE was intra-abdominal venous thrombosis or vascular access-induced thrombosis, or if anticoagulation therapy was not instituted. Pts were also excluded if they were lost to follow-up within 1 week after initiating anticoagulation therapy. Maximal duration of anticoagulation therapy was 12 months and pts in whom anticoagulation therapy was stopped within 12 months were censored at the time of discontinuation. Results A total of 456 pts were included in this analysis. The median age was 65 (range, 27–91) years and 249 pts (55%) were male. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 185 pts (41%). The primary sites of tumor were breast in 22 (5%), genito-urinary tracts in 38 (8%), esophago-gastric in 76 (17%), colo-rectum in 81 (18%), hepato-biliary tracts in 37 (8%), pancreas in 66 (15%), and lung in 136 (30%). Palliative chemotherapy was administered in 328 pts (72%). The location of index VTE was isolated pulmonary embolism (PE) in 196 (43%), isolated lower-extremity deep venous thrombosis (DVT) in 169 (37%), and concomitant PE and DVT in 91 (20%). For initial anticoagulation therapy, low molecular weight heparin was administered in 362 pts (79%), and for long-term therapy, 306 pts (75%) received warfarin. The median duration of anticoagulation therapy after index VTE was 2.4 (range, 0.1–58.3) months. The 6-months and 12-month cumulative incidences of recurrent VTE were 22.4% (95% CI, 19.4–25.4) and 28.7% (95% CI, 24.0–33.4), respectively. In the multivariate analysis for identifying the risk factors associated with the development of recurrent VTE, pancreas (HR, 6.12; 95% CI, 2.00–18.73) and lung (HR, 2.98; 95% CI, 1.03–8.58) as the primary tumor site, poor ECOG PS (HR, 1.74; 95% CI, 1.14–2.67) and VTE initially presented with PE (HR, 2.29; 95% CI, 1.17–4.47) were independent risk factors for increased risk of recurrent VTE. With a median follow-up of 29.1 (range, 1.0–91.2) months, median OS was 11.9 (95% CI, 10.2–13.6) months. Pts with recurrent VTE had a significantly shorter OS than those without recurrent VTE (median, 8.4 vs. 13.0 months, P Conclusion Although Asian populations are thought to have lower risk for developing recurrent VTE, our study demonstrates that the incidence of recurrent VTE in pts with advanced solid cancers is comparable to that of Western populations. Lung or pancreas as a primary tumor site, poor PS, and initial presentation with PE are independent risk factors for recurrent VTE. Additionally, survival is adversely affected by recurrent VTE. Further studies are needed to validate the results of our study and to optimize the treatment strategies for improving treatment outcomes in advanced cancer pts. Disclosures: No relevant conflicts of interest to declare.

Background The prevalence of monoclonal gammopathy of undetermined significance (MGUS) increases with patient age and varies by race. However, reliable data on the epidemiology of MGUS is limited in Korea. We previously reported the prevalence of MGUS among 1000 participants of a Korean Elderly Urban Cohort recruited from 2005 to 2006 (First Wave, Park HK Am J Hematol . 2011;86:752-5); age and gender-adjusted prevalence of MGUS was estimated as 3.3% (95% confidence interval [CI] = 2.0-4.6%). Here, we report the five years’ follow-up study for frequency of MGUS between 2010 and 2011. Methods Korean Longitudinal Study on Health and Aging (KLoSHA) is a population-based, prospective cohort study of health, aging, and common geriatric diseases in a population aged ≥ 65 years in Seongnam-si, a satellite city of Seoul. Of the random sample of 1118 candidates from 61,730 Korean elderly individuals, 698 respondents agreed to participate in baseline KLoSHA study between 2005 and 2006. A total of 680 with available samples were screened for MGUS. We followed them and collected their serum between 2010 and 2011 (Second Wave). The screening of MGUS in the Second Wave was performed using serum protein electrophoresis followed by immunofixation assays; MGUS was defined by the presence of a serum monoclonal protein (M-protein), at a concentration Results Of the 680 respondents (21 with MGUS, 659 without MGUS) in the First Wave, 361 (53%) agreed to participate in the Second Wave. Causes of nonattendance were death in 20%, refusal in 19%, move to other area in 6%, and loss to contact in 3%. Of the 361 respondents, 10 were identified to have MGUS. Overall frequency of MGUS is 2.8% (95% CI: 1.3 - 5.0%). Among 21 patients with MGUS in the First Wave, 9 were followed up in the Second Wave. Six of them showed persistent MGUS. One of them showed mild anemia with persistent M-protein of 1.4g/dL suggestive of progression to multiple myeloma, but was not confirmed because of early death just after screening. Interestingly, M-protein was disappeared in remaining 2 patients with MGUS in the First wave. Among 659 respondents without MGUS in the First Wave, 352 were followed up in the Second Wave. Four of them were newly diagnosed with MGUS. In Kaplan-Meier survival analysis, there was no significant difference of survival between respondents with MGUS and without MGUS in the First Wave ( P = 0.66 by Log-rank test). Conclusion Five years’ follow-up data showed the natural clinical course of MGUS. The diagnosis of MGUS was not associated with an increased risk of death in Korean elderly population. The interesting finding was that M-protein was disappeared in some patients with MGUS. High rate of non-attendance (47%) in Second Wave is the major limitation. Disclosures: No relevant conflicts of interest to declare.

Abstract 5170 Iron deficiency (ID) is the most important cause of anemia in the world. The contribution of ID to anemia and causes of iron deficiency anemia (IDA) is heterogeneous between different populations. We analyzed the prevalence and risk factors of iron deficiency anemia among participants of the fifth Korean Health and Nutrition Examination Survey in 2010 (KNHANES V-1). In this survey, stratified, multistaged, probability-sampling designs and weighting adjustments were conducted to represent the entire Korean population. Anemia was defined in accordance to WHO criteria: Hemoglobin (Hb) less than 11. 5 g/dL in aged 10 to 11 years, less than 12. 0 in aged 12 to 14 years, less than 13 g/dL in men >15 years, and less than 12 g/dL in non-pregnant women. ID was defined as a transferrin saturation lower than 10% or serum ferritin levels lower than 15 μg/L. IDA was confirmed with concomittent anemia with ID. Persons with active malignancy were excluded. In addition to age and sex, we analyzed the correlation between IDA and individual socioeconomic status including income, education and marriage, nutritional status based on Korean dietary reference intakes, body mass index, eating habits, body weight changes and so on. In a total of 6689 (3010 men and 3679 women) over 10 years of age, the prevalence of IDA was 0. 82% (95% CI 0. 25–1. 39) for men and 8. 01% (6. 84–9. 18) for women. (p 65 years). IDA prevalence in the elderly had no significant sexual difference. (0. 78 % in men and 1. 21% in women aged 65 to 74 years, 4. 11% in men and 4. 92 % in women aged > 75 years). IDA was more prevalent in persons with low income (the bottom 25% of participants vs others, 5. 6% vs 4. 2%, p=0. 024), high education level (at least a high school graduate vs others, 5. 3% vs 2. 4%, p=0. 0002), low BMI (mass(kg)/((height(m))2) ( Disclosures: No relevant conflicts of interest to declare.

7566 Background: Other than in-frame deletional mutation (MT) in exon 19 and Leu858Arg point MT in EGFR gene, there are many rare and complex MT. The purpose of this study was to investigate was to clarify the clinical significance of rare and complex MT, and the efficacy of EGFR TKI in these patients. Methods: Rare MTs were defined any MT other than deletional MT in exon 19, Leu858Arg in exon 21, and Thr790Met in exon 20. Complex MT was defined two different EGFR MTs co-occurring within the single tumor sample. We have analyzed consecutive database of NSCLC patients who were treated with either gefitinib or erlotinib at Seoul National University Hospital between Jan. 2002 and Dec. 2011. For analysis of EGFR MT, coding sequences from exon 18 to 21 were amplified by nested PCR and subjected to direct sequencing methods. Results: Among the 1,159 TKI treated patients, 301 patients had EGFR MT (177 patients (58.8%) with del-19, 104 patients (34.6%) with Leu858Arg, and 20 patients (6.6%) with rare MT). Twenty-three (7.6%) patients have complex MT, and 55 (18.3%) patients have Gln787Gln polymorphism particularly associated with Leu858Arg MT. Identified rare MT were follows; exon 18: Leu692Phe, Glu707Lys, Glu709Gly, Lys714Asn, Gly7Ala, Thr725Thr, exon 19: Ala755Asp Lys737Thr, exon 20: Val786Met, exon21: Ala871Gly, Gly873Gln, Leu833Val, Val834Leu, Arg836Cys, Pro848Leu, Ala859Thr, Leu861Gln. When categorizing 3 groups (group A: classic MT alone, group B: complex MT with classic + rare MT, group C: rare MT alone or complex MT with rare MTs), response rate (RR) to TKI was different between each groups (RR= 78.7% in group A vs. 69.2% in group B vs. 38.5% in group C, respectively, P < 0.001). Progression-free survival (PFS) was also poorer in rare MT (median PFS: 12.1 mo vs. 7.6 mo vs. 2.1 mo, respectively, P= 0.020,). Gln787Gln polymorphism of exon 21 was not associated with RR or PFS (P= 0.101, P= 146, respectively) Conclusions: In this large case series, NSCLC patients who harboring rare MT other than del-19 and Leu858Arg, does not seems response to EGFR TKI. However, complex MT with the classical MT showed similar treatment efficacy toward EGFR TKI with that of classical MT alone.

목 적 : 개별 혈청과 혼합 혈청을 이용한 immunoblotting을 비교함으로써 유전자 재조합 식품에 새로이 발현된 단백질에 대한 혈청 선별 검사에서 개별 혈청 대신 혼합 혈청을 사용할 수 있을지를 알아보고자 하였다. 방 법 : ImmunoCAP (Pharmacia, Uppsala, Sweden) 검사상 난백 특이 immunoglobulin E (IgE)에 양성을 보인 환아 15명과 땅콩 특이 IgE에 양성을 보인 환아 12명의 혈청을 확보하였다. 특이 IgE 수준에 따른 반응의 차이를 비교하기 위해 환자의 땅콩 특이 IgE 수준이 10 kU/L이하와 10kU/L 이상, 계란은 5 kU/L 미만, 5-10 kU/L, 11kU/L 이상으로 나누어 땅콩 및 난백 단백질 추출물과 immuno-blotting을 실시하였다. 결 과: 땅콩 특이 IgE 수준이 10 kU/L 이상이나 이하에 상관 없이 개별 혈청에서 반응하였던 단백질이 혼합 혈청과의 반응에서도 모두 선명하게 감지되었다. 난백 특이 IgE 양성인 혈청과 난백과의 반응에서도 특이 IgE 수준에 관계없이 모든 군에서 개별 혈청에 나타났던 양성 반응을 혼합 혈청에서도 확인할 수 있었다. 결 론 : 혈청 내 특이 IgE와 특정 단백질 간의 반응성을 관찰하는 데에는 특이 IgE 값에 관계없이 개별 혈청 대신 혼합 혈청을 사용해도 될 것으로 판단된다.

Regional dietary habits and cooking methods affect the prevalence of specific food allergies; therefore, we determined the effects of various pH conditions on major peanut allergens. Peanut kernels were soaked overnight in commercial vinegar (pH 2.3) or acetic acid solutions at pH 1.0, 3.0, or 5.0. Protein extracts from the sera of seven patients with peanut-specific IgE levels15 kU(A)/L were analyzed by SDS-PAGE and immunolabeling. A densitometer was used to quantify and compare the allergenicity of each protein. The density of Ara h 1 was reduced by treatment with pH 1.0, 3.0, or 5.0 acetic acid, or commercial vinegar. Ara h 2 remained largely unchanged after treatment with pH 5.0 acetic acid, and was decreased following treatment with pH 1.0, 2.3, or 3.0 acetic acid. Ara h 3 and Ara h 6 appeared as a thick band after treatment with pH 1.0 acetic acid and commercial vinegar. IgE-binding intensities to Ara h 1, Ara h 2, and Ara h 3 were significantly reduced after treatment with pH 1.0 acetic acid or commercial vinegar. These data suggest that treatment with acetic acid at various pH values affects peanut allergenicity and may explain the low prevalence of peanut allergy in Korea.

Abstract 3355 Introduction: Cancer patients (pts) with venous thromboembolism (VTE) have an increased risk of VTE recurrence. However, few data are available regarding the incidence, impact of malignancy characteristics on VTE recurrence in pts with recurrent/metastatic solid cancer. Reliable information on the factors determining the risk of VTE recurrence may facilitate tailored anticoagulation therapy by discriminating cancer-associated VTE pts according to the risk of recurrence. Therefore, the aims of this study are to investigate the incidence of VTE recurrence, its association with malignancy characteristics, and prognostic factors for VTE recurrence in pts with recurrent/metastatic solid cancer receiving anticoagulation therapy after prior index VTE. Methods: The data source in this study is a web-based registry of Korean VTE Working Party (http://kdvt.chamc.co.kr), which is an ongoing, multicenter database system recruiting consecutive patients with VTE confirmed by objective tests. The pts were eligible to enter the study cohort if they had received a diagnosis of recurrent/metastatic solid cancer between May 2005 and Dec 2010 and initiated anticoagulation therapy after the diagnosis of index VTE. Pts were excluded from the study cohort if they had received a diagnosis of hematologic malignancies, if solid cancers were not recurrent or metastatic disease, if index VTE was intra-abdominal venous thrombosis (IVT) or vascular access-induced thrombosis, or if anticoagulation therapy was not instituted. The period of follow-up considered for the analysis was the duration of anticoagulation therapy with a maximum of 6 months and pts in whom anticoagulation therapy was stopped within 6 months were censored at the time of treatment cessation. Results: The data of 363 recurrent/metastatic solid cancer pts with anticoagulation therapy following the diagnosis of index VTE were analyzed. The median age was 65 (range, 27–91) years and 201 pts (55%) were male. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 164 pts (55%). The primary sites of cancer were breast in 17 pts, genito-urinary tract in 36, stomach-esophagus in 74, colo-rectum in 81, hepato-biliary tract in 28, pancreas in 34, and lung in 93. Two hundred sixty (72%) pts received active systemic chemotherapy. The location of index VTE was isolated pulmonary embolism (PE) in 151 (42%), isolated deep venous thrombosis (DVT) in 136 (37%), and combined PE and DVT in 76 (21%). The type of anticoagulation therapy for initial therapy was low molecular weight heparin in 282 pts (78%), and for long-term therapy was warfarin in 272 (75%). Eighteen (5%) pts received systemic or catheter-directed thrombolytic therapy for their index VTE at the time of initial diagnosis. Median duration of anticoagulation therapy was 2.4 months (range, 0.1–6.0). Fifty four (15%) pts presented with VTE recurrence within the first 6 months of index VTE. The distribution of site at VTE recurrence was 32 (57%) isolated PE, 10 (18%) isolated extremity DVT, 1 (2%) isolated IVT, 10 (18%) combined PE and DVT, 2 (4%) combined DVT and IVT, and 1 (2%) combined PE/DVT and IVT. The 6-month cumulative incidence of VTE recurrence after index VTE was 26.6% (95% CI, 19.7–33.5). In the univariate analysis for cumulative incidence of VTE recurrence, male gender (P=0.022), 2 to 4 of ECOG PS (P=0.002), lung or pancreas of primary site of cancer (P Conclusion: This study demonstrated that the risk of VTE recurrence in Asian patients with recurrent/metastatic solid cancer receiving anticoagulation therapy after prior VTE was substantially high. Pancreas or lung as a cancer site, poor PS, and male gender were strong predictors of VTE recurrence. These may provide basic information to optimize treatment strategies for tailored thromboprophylaxis in recurrent or metastatic solid cancer pts. Further larger studies are needed to confirm our results and to compare with different ethnicities. Disclosures: No relevant conflicts of interest to declare.

Abstract 4983 Background: Primary gastrointestinal (GI) lymphoma is the most commonly involved extranodal site and represents 10–15% of all Non-Hodgkin's Lymphoma cases. Recent studies showed that the prognostic value of early 18F-FDG PET using maximum standardized uptake volume (SUVmax) on pretreatment was important prognostic factor in primary GI diffuse large B cell lymphoma (DLBCL). However, initial tumor burden is still an important subject associated with prognosis even extranodal DLBCL. The purpose of this study was to assess the prognostic impact of metabolic tumor volume (MTV) as tumor burden using by PET scan technique compared with initial SUVmax in primary GI DLBCL. Patients and methods: From April, 2006 to July, 2009, 125 stage IE (58 patients) or IIE (67 patients) primary GI DLBCL patients with localized lymph node involvement were enrolled and assigned to 6 or 8 cycles of R-CHOP therapy. Median follow-up was 36 months. Median age was 62 years (range, 20–79 years). Seventy-four patients were male and remainders were female. Numbers of patients above 60 years were 71. Twenty-five patients had an Eastern Cooperative Oncology Group performance status of more than two. Calculatory system by computer automatically delineated a extranodal target lesions above SUV, 2.5 and MTV of GI lesion was 3-dimensional reconstructed by fusion software. The SUVmax was collected from predominant GI lesion and calculated based on the attenuation-corrected images, the amount of injected 18F-FDG and body weight. Results: The extranodal sites of GI tract were included stomach and duodenum (64 patients, 51.2%), jejunum (10 patients, 8%), terminal ileum (30 patients, 24%), cecum (7 patients, 5.6%), ascending colon (8 patients, 6.4%), transverse colon (3 patients, 2.4%) and decending colon (3 patients, 2.4%). We used ROC curve analysis. 158.3cm3 was decided as best ideal cut-off value of MTV and 15.5 was decided as the cut-off value of SUVmax. Several factors (age, sex, disease status and IPI score) between high MTV (≥158.3cm3) and low MTV group ( Conclusion: In primary GI DLBCL, high MTV is very important and potential prognostic factor compared with SUVmax for predicting the survival. Therefore, more aggressive treatment strategy would be performed in primary GI DLBCL patients having initial high tumor burden. Disclosures: No relevant conflicts of interest to declare.

Catechin improves endothelial dysfunction by reducing NADPH oxidase activity in prediabetic stage of type 2 diabetic rat model Sang-Hyun Ihma,∗, Kiyuk Changa, Ho-Joong Youna, KiBae Seunga, Youn Jeong Kimb, Min-Ho Oakc, Jeong-Ok Leec a Division of Cradiology, The Catholic University Of Korea, Seoul, South Korea b Department of Radiology, Inha University Hospital, Incheon, South Korea c Research andDevelopmentCenter, Yangji Chemicals, Su-won, South Korea