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Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.

// Muhammad Shahid 1, * , Kyoung Min Cho 2, * , Minh Nam Nguyen 3 , Tae Gyu Choi 3 , Yong Hwa Jo 3 , Saurav Nath Aryal 1 , Ji Youn Yoo 1 , Hyeong Rok Yun 1 , Jae Woong Lee 1 , Young Gyu Eun 4 , Ju-Seog Lee 5 , Insug Kang 1, 3 , Joohun Ha 1, 3 , Hwi-Joong Yoon 2 , Si-Young Kim 2 , Sung Soo Kim 1, 3 1 Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea 2 Department of Internal Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea 3 Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea 4 Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, Seoul, Republic of Korea 5 Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence to: Sung Soo Kim, email: sgskim@khu.ac.kr Keywords: glioma, gene expression profile, prognosis, chemosensitivity Received: March 03, 2016 Accepted: May 20, 2016 Published: June 13, 2016 ABSTRACT Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma’s prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

TO THE EDITOR: We read an interesting paper by Shin et al. [1] in a recent issue of Blood Research, titled "Chronic eosinophilic leukemia (CEL) with a FIP1L1-PDGFRA rearrangement: Two case reports and a review of Korean cases". To our knowledge, CEL with FIP1L1-PDGFRA rearrangement is very rare in Korea, and only 4 cases have been reported to date [1,2,3] (Table 1). In this letter, we report an additional rare case of CEL with FIP1L1-PDGFRA rearrangement and briefly discuss the possibilities of ethnical differences of this rare gene rearrangement, specifically in the Korean population.

A symbiotic mutant of Lotus japonicus, called sunergos1-1 (suner1-1), originated from a har1-1 suppressor screen. suner1-1 supports epidermal infection by Mesorhizobium loti and initiates cell divisions for nodule primordia organogenesis. However, these processes appear to be temporarily stalled early during symbiotic interaction leading to a low nodule number phenotype. This defect is ephemeral and near wild-type nodule numbers are reached by suner1-1 at a later point after infection. Using an approach that combined map-based cloning and next-generation sequencing, we have identified the causative mutation and show that the suner1-1 phenotype is determined by a weak recessive allele, with the corresponding wild-type SUNER1 locus encoding a predicted subunit A of a DNA topoisomerase VI. Our data suggest that at least one function of SUNER1 during symbiosis is to participate in endoreduplication, which is an essential step during normal differentiation of functional, nitrogen-fixing nodules. This article is protected by copyright. All rights reserved.

Background Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). Study Design and Methods This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. Results A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p = 0.02366) and AA (p = 0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p = 0.002 and p = 0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. Conclusions This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML). All-trans retinoic acid (ATRA) is an effective drug in the treatment of APL by promoting the terminal differentiation of leukemic cells into phenotypically mature myeloid cells. The microgranular-variant APL counts for a quarter of APL and is similar to monocytic origin leukemia. The microgranular-variant type has no effect on APL treatment. ATRA is related with some serious side effects such as Sweet’s syndrome and retinoic acid syndrome (RAS). Histologic characteristics of RAS are seen in capillary leakage and infiltration of organs by mature myeloid cells. ATRA-induced myositis is rarely described in adults and rare in children with APL. There have been increasing reports of ATRA-induced myositis, with its frequent association with RAS and Sweet’s syndrome. We report a patient with ATRA-induced myositis and RAS in microgranular variant APL and review the previously reported cases in the literature of ATRA-induced myositis. * APL : acute promyelocytic leukemia; ATRA : all-trans retinoic acid; RAS : retinoic acid syndrome; FISH : fluorescence in situ hybridization; MRI : magnetic resonance imaging; CK : creatine kinase; ICU : intensive care unit; CT : computed tomography; WBC : white blood cell

Monocloncal protein (M-protein) is a cloncal immnoglobulin produced by malignant plasma cells. It is not uncommon to detect more than 1 M-protein in multiple myeloma (MM) and this can stem from 2 kinds of M-proteins produced by a single B cell clone or from 2 separate clones. Herein, we report our detection, via urine immunoelectrophoresis, of 2 κ light chain peaks in a 77-year-old female patient with MM. The patient without significant adverse events in her medical history presented with clavicular fracture and was admitted to the Department of Orthopedics. There was no remarkable laboratory findings except a significant elevation of κ free light chain (FLC) and FLC ratio. After 10 months, bone marrow showed increased plasma cells in touch imprints and urine capillary electrophoresis revealed 2 separate peaks in the gamma region, which were found to be κ light chain (LC) via immunotyping. We found 2 separate FLCs in our patient that were not detected initially by immunoelectrophoresis, but were found during follow-up with BM examination; elevated LCs had previously been detected via FLC analysis. * MM : multiple myeloma; BM : bone-marrow; Igs : immunoglobulins; M-proteins : monoclonal proteins; CBC : complete blood count; Hb : hemoglobin; BUN : blood urea nitrogen; GE : gel electrophoresis; FLC : free light chain; rFLC : FLC ratio; CE : capillary electrophoresis

Plasma cell myeloma (PCM) is a malignant hematologic disease characterized by the proliferation of neoplastic plasma cells, producing excessive amounts of monoclonal immunoglobulin (Ig) or light chain (LC) [1, 2]. Although plasma cells are widely distributed throughout the body, PCM is found most often within the bone and bone marrow (BM), while the dissemination of extramedullary plasmacytoma into the lung has been reported to be very rare [3]. Moreover, pleural effusion caused by myelomatous involvement such as myelomatous pleural effusion (MPE) occurs in less than 1% of PCM cases [4-6]. We report a case of PCM with a rare presentation of MPE and plasmacytoma mimicking lung cancer. This case is characterized by the presence of monoclonal Ig using electrophoresis and free light chain (FLC) assay in addition to cytologic examination of the pleural fluid [7]. A 59-yr-old Korean woman complaining of anorexia and weight loss for 6 weeks was referred to our hospital in order to evaluate an incidental finding of a lung mass during a routine check-up from a local clinic. The patient had no history of smoking and exposure to environmental asbestos. Results of routine blood tests were as follows: Hb, 8.9 g/dL; platelet count, 199×109/L; and white blood cell (WBC), 3.8×109/L (segmented neutrophil, 79%; lymphocyte, 18%; monocyte, 2%; and eosinophil, 1%); and approximately 1 nucleated red blood cell (RBC) per 100 WBCs. Results of biochemical tests were as follows: protein, 6.4 g/dL (reference range, 5.8-8.0 g/dL); albumin, 4.4 g/dL (reference range, 3.1-5.2 g/dL); creatinine, 0.4 mg/dL (reference range, 0.6-1.2 g/dL); and lactate dehydrogenase, 602 U/L (reference range, 218-472 U/L). The chest computed tomography (CT) examination presented a lung mass with a lobulated contour in the left lower lobe, a bony destructive soft tissue mass in the left ribs, and multifocal pre/paravertebral mass lesions, especially at the T9-L1 level, with pleural effusions (Fig. 1). Radiologic findings suggested lung cancer with pleural metastasis, or alternatively, a PCM. Positron emission tomography (PET)/CT and bone scintigraphy showed multiple hypermetabolic lesions in the lung adjacent to the left ribs, which suggested lung cancer with multiple bone metastases and a recommendation to rule out all metastases of unknown origin. Cytologic examination of the pleural fluid revealed a large number of plasma cells. In the FLC assay, serum lambda FLC increased to 183 mg/L (reference range, 5.71-26.3 mg/L), and the kappa/lambda FLC ratio (rFLC) was markedly reversed to 0.048 (reference range, 0.26-1.65). Capillary electrophoresis with serum and urine samples showed a discrete peak with a definite immunosubtraction in lambda LC, suggesting monoclonal gammopathy. In the pleural fluid, gel electrophoresis revealed a monoclonal band in lambda antisera and lambda FLC was measured at 14,000.0 mg/L. BM examination revealed 18.6% plasma cells with eccentric nuclei and basophilic cytoplasm, and biopsy sections showed a packed marrow (Fig. 2). Surgery was performed for excision of the pleural mass on the day after BM examination (Fig. 3). Immunohistochemical stains on sections from biopsy specimens from the left pleural mass were compatible with plasmacytoma as follows: cytokeratin (CK) (-),CD5 (-), CD45 (+), CD138 (+), kappa (-), and lambda (+).Based on these results, the patient was diagnosed as having PCM with extramedullary dissemination into the lung. The patient was referred to the hematology department for chemotherapy, and peripheral blood stem cells were collected for an autologous stem cell transplant thereafter. Fig. 1 Imaging studies. Computed tomography (CT) and positron emission tomography (PET)/CT findings showing the branching out lung mass (A), pleural nodules (B), and paraspinal lesions (C), which were initially interpreted to be suggestive of lung cancer with ... Fig. 2 Bone marrow findings. Plasma cells with eccentric nuclei and basophilic cytoplasm were predominantly observed in aspiration smears (A, Wright stain, ×1,000) and clot sections (B, H&E stain, ×1,000). The biopsy sections revealed ... Fig. 3 Examinations of the pleural fluid and biopsy. In the cytospin of pleural fluid, plasma cells characterized by basophilic cytoplasm, eccentric nucleus and perinuclear halo were predominantly observed (A, Wright stain, ×1,000). In the pleural biopsy, ... Classically, PCM occurs mainly in BM-rich bone [8]. Therefore, primary clinical presentation includes bone pain, pathological fractures, and anemia [5, 9]. Extramedullary plasmacytomas have been reported in 15-20% of patients at diagnosis and in an additional 15% during the course of PCM, and these patients are often associated with high-risk diseases like MPE [4]. Although hematopoietic neoplasms may frequently colonize the pleural tissue, such as malignant lymphoma, especially in the end stage of the disease, extramedullary existence of plasmacytoma is not common and the incidence of thoracic cases is low, especially in patients presenting with pulmonary plasmacytoma and MPE to simulate a pleural mesothelioma or lung cancer [8, 10-12]. This study is limited in that IgD and IgE were not measured in further tests, because this was a retrospective case review. We report here a unique presentation of PCM overlapping massive pleural effusion to include monoclonal components and pleural plasmacytoma as initially mistaken for lung cancer. When MPE and pleural involvement are concomitantly observed, as in this case, a precise diagnosis of PCM is difficult when only clinical and imaging studies are conducted. In order to discriminate extramedullary PCM from other malignancies, biochemical assays such as electrophoresis or FLC assay in body fluid are very helpful to confirm the presence of monoclonal components when performed along with cytologic examinations of the pleural fluid.

As polymerase chain reaction (PCR) is increasingly applied in clinical medicine, early detection and more accurate diagnosis is possible. Using molecular methods with cerebrospinal fluid (CSF) samples in addition to existing cytological methods is of value even if only occult malignant cells are present. We describe a case of central nervous system (CNS) leukemia in a patient with Philadelphia chromosome–positive acute lymphoblastic leukemia confirmed by reverse transcription PCR (RT-PCR) in a CSF specimen from a patient who was treated with chemotherapy (Hyper CVAD protocol, including cyclophosphamide, vincristine, adriamycin, prednisolone, and intrathecal methotrexate). Study of her CSF identified atypical lymphocytes. To ensure that the diagnosis was correct, we conducted a CSF exam using RT-PCR and confirmed CNS relapse by identifying the BCR-ABL gene. After remission, a CNS relapse occurred in the form of optic nerve involvement. Despite treatment, the patient died of leukemia progression and multiple organ failure with sepsis. We discuss the diagnostic role of RT-PCR with CSF samples for early and accurate detection of CNS relapse and review the relevant literature on this subject.

An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet counts of 27 × 10(9)/L, and white blood cell counts of 85.33 × 10(9)/L with 55% blasts. Peripheral blood samples were used in all the tests, as bone marrow examination could not be performed because of the patient's extremely advanced age and poor general health condition. Flow cytometric analysis, chromosome analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this is the second most elderly de novo AML patient associated with t(3;21) to be reported.

Among patients with acute promyelocytic leukemia (APL), 10% to 30% experience relapse. Most relapses occur within 2 years; only a few, known as late relapses, occur 4 years after achievement of the first complete remission (CR). We present a rare case of an ethnic Asian patient with APL who experienced late relapse, which has been continuously monitored by reverse transcription polymerase chain reaction (RT-PCR) for long-term molecular remission. Recently, the European APL Group published 2 large-scale studies related to laterelapse APL; however, only 2 Asian cases of late-relapse APL had previously been documented in the literature. We consider this case to be the first report of a patient with late-relapse APL in South Korea and believe that future studies of late-relapse APL for Asian and other ethnic groups are necessary.

Stomach cancer is still one of the most prevalent malignancies and is the main cause of cancer deaths worldwide. The outcome for patients with metastasis, as well as for those with tumor recurrence, is dismal, with median survival time not greater than a year. Patients with unresectable locally advanced or metastatic lesions have been treated with systemic chemotherapy, and several randomized studies have demonstrated the benefit of chemotherapy compared with best supportive care. Recently, randomized phase III trials have presented a benefit of second-line chemotherapy compared with supportive care alone. However, it is not known at present which drug is the most effective in this setting. In Korea, the practice of offering second-line treatment to patients with advanced gastric cancer (AGC) is common, and many prospective clinical trials investigating clinical outcomes of second-line chemotherapy have been reported. Therefore, to define the potential role of second-line chemotherapy and to help to select an effective regimen, we review the published Korean prospective data concerning the use of chemotherapy in the second-line setting for the treatment of AGC. No phase III trials but 20 phase II trials were identified. The benefit of second-line chemotherapy in AGC has indirect evidence considering prolongation of progression-free survival (PFS) and improvement of the response rate. Taxanes, irinotecan, and oxaliplatin have been studied much and might be promising drugs considering cross-resistance to a 5-fluorouracil and cisplatin combination (FP). A large, prospective, multicenter, randomized phase III study is warranted to select the most effective second-line chemotherapeutic agents.

We characterized the cytogenetic changes and prognostic characteristics of 133 Korean patients with myelodysplastic syndrome (MDS), focusing on 5q- syndrome and MDS with chromosome abnormalities involving 5q deletion according to World Health Organization 2008 classification. In all patients, G banding and fluorescence in situ hybridization for 5q were performed, and in MDS patients with 5q deletion, the deleted region on chromosome 5 was mapped with fluorescence in situ hybridization for EGR1, CSF1R, and PDGFRB. The frequency of isolated del(5q) syndrome and 5q deletion was 2.2% (3 of 137 patients) and 15.3% (21 of 137 patients), respectively. International Prognostic Scoring System (IPSS) groups were low risk (5.8%), intermediate 1 (51.1%), intermediate 2 (27.8%), and high risk (15.3%). The patients with del(5q) were significantly older (62 years) and showed an unfavorable survival compared to patients without del(5q). Half (53%) of the patients with del(5q) also had complex chromosome abnormalities, including chromosome 7 abnormalities. Of the patients with del(5q), 93.3% were deleted for all three regions on 5q, compared to 66.7% of patients with isolated del(5q). Marker chromosomes proved to be chromosome 5 with interstitial deletion of q arm by fluorescence in situ hybridization in three patients. The biological characteristics of MDS in Korea seem to be markedly different from those of Caucasians, with Koreans having a younger age, lower frequencies of 5q- syndrome, higher frequencies of complex cytogenetic abnormalities including del(5q), and poorer prognosis. We infer that additional chromosome abnormalities contribute to the adverse prognostic impact in patients with del(5q).

The frequency of thromboembolic events (TE) in Caucasian patients with multiple myeloma (MM) receiving thalidomide as the initial treatment has been reported to be 10~58% without prophylactic anticoagulation. Korean MM patients treated with thalidomide were studied to determine the frequency of TE and associated risk factors. A retrospective medical record review of the Korean MM registry from 25 centers in Korea between 2003 and 2007 was performed. We assessed the incidence of arterial and venous TE and the associated clinical parameters. Three hundred and sixty MM patients (median age 61 years, range 32-88 years) received thalidomide treatment. Fourteen patients (3.9%) developed TE: 12 had venous and two had arterial locations. The sites for the venous TE included lungs (seven), lower extremities (four), upper extremities (one), and neck (one). Arterial TE developed in cerebral and peripheral arteries each. No single clinical parameter such as prerequisite for the metabolic syndrome, disease status, and treatment regimen were predictive for the development of TE. The frequency of TE in patients who received thalidomide as initial therapy (7/155) was not different from those who received thalidomide for progressive or relapsed disease (7/205, p = 0.592). The frequency of TE during thalidomide treatment in Korean patients with MM was low. No significant clinical factor was found to be a risk factor. The subgroup requiring thromboprophylaxis among the Korean patients with MM, receiving thalidomide, needs to be clarified.

Aim: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. Methods: We retrospectively analyzed registered data from 3,209 patients since 1999. Results: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20–54.06 months). Patients ≤40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. Conclusions: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.

SummaryEvaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients’ diagnoses were essential thrombocythemia (ET n=146), polycythemia vera (PV n=120), primary myelofibrosis (n=12), and unclassifiable MPN (MPNu n=5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p=0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p=0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

Purpose Fentanyl is a synthetic opioid and transdermal therapeutic system (TTS), designed to release the drug into the skin at a constant rate, ranging from 25 to 100 microgram/hr, for up to 3 days. For the control of chronic cancer pain, Durogesic(R) patches (Janssen Co., USA) are now widely used. Recently, the Hana Company in Korea developed a new fentanyl patch, Fentas(R) using a different method. To compare the efficacy, and safety, of the fentanyl patch manufactured in Korea (Hana Pharm. Co. Ltd), with the Durogesic(R) patch, in controlling cancer pain, we performed randomized controlled, open labelled, phase III studies. MATERIALS AND METGODS: From January 2000 to April 2001, 85 patients were enrolled, 69 of whom (42 in D arm and 43 in F arm) completed the study, and were therefore assessable for per protocol (PP) analyses. Results There were no significant differences between the two groups in baseline characteristics, with the exception of age. The primary end point was to show the therapeutic equivalence of the two patches. In these clinical trials, the confidence interval of difference, between the test drug (Fentas(R)) and the control (Durogesic(R)), was 0.027~ +0.124 by intention to treat (ITT) analysis. Even if the upper confidence interval exceeds + 0.1, the test drug is not superior to the control drug, because the confidence interval includes 0. However, by PP analysis, the confidence interval lies exactly within +/- 0.1. Therefore, we could conclude the two patches are therapeutically equivalent. The second endpoint was the difference of visual analog scale (VAS) between the baseline and the average of three measurements after treatment. The difference in VAS was 50.44+/-10.28 for the F arm, and 44.69+/-11.00 for the D arm. By PP analysis the test drug was superior to the control (p=0.028). The rescue morphine amount was 81.21+/-124.76 for F arm and 66.19+/-115.9 for D arm, and there was no significant difference between the two groups (p=0.6063). The most common adverse effects of both fentanyl patches were nausea or vomiting (55.3%), somnolence (50.0%), constipation (39.5%), gastrointestinal discomfort (57.9%) and headaches (25.0%). In general there was no significant difference in side effects or laboratory data between the two groups. Conclusion These findings suggest that Fentas(R) patches, administered every 3 days, are effective, safe, and well tolerated for the treatment of most patients with cancer pain and is as effective or better than Durogesic(R).

Purpose: Many studies have shown that angiogenesis has an important role in the growth, progression, and metastasis of solid tumors. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, we investigated the prognostic significance of the expression of VEGF in patients with an advanced gastric carcinoma. Materials and Methods: Specimens from 54 gastric adenocarcinoma patients were stained using a polyclonal antibody against VEGF. Correlations of the expression of VEGF, microvessel density, and various other clinicopathological factors were analysed. Results: Seventeen (31.5%) and 37 cases (68.5%) were VEGF-negative and positive, respectively. There was significant correlation between the expression of VEGF and pathological differentiation. There were no significant correlations between the expression of VEGF, stage and recurrence of a gastric carcinoma. The microvessel density was significantly higher in the VEGF-positive than the VEGF-negative tumors. Survivals of the VEGF-negative patients were significantly prolonged compared to those of the VEGF-positive patients. Conclusion: The results of this study show that the expression of VEGF may be a useful prognostic factor for patients with a gastric adenocarcinoma.

The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8 %, 238/2717), but t(15;17) showed an almost same number (8.6 %,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7 %). The most common French-American-British (FAB) classification type was M2 (32.2 %), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1 % of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (n = 45, 15.9 %) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15 %. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.

The effectiveness of the tumor necrosis-α (TNF-α) blockade has changed the treatment of several chronic inflammatory diseases, including inflammatory bowel disease; however, this treatment also has disadvantages. The use of immunosuppressants in combination with infliximab has been associated with greater risk of developing malignant neoplasms. Herein, we report the case of a 33-year-old ethnic Korean man with Crohn disease (CD) who developed papillary thyroid carcinoma (PTC) and, subsequently, T-cell acute lymphoblastic leukemia (ALL) after approximately 16.0 years of immunosuppressant therapy and 5.5 years of infliximab therapy. To our knowledge, this is the first case described in the literature of 2 different malignant neoplasms, 1 of hematologic origin and the other involving the solid organs, in a patient with CD. Through a systematic literature review, we found 28 cases of acute leukemia in adult patients with CD, of whom 22 had myeloid leukemia and 6 had lymphoid leukemia. Half of the patients with ALL underwent TNF-α-blocker therapy in combination with thiopurines.

The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0–10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of borte-zomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.

Monoclonal immunoglobulin, as a marker for monoclonal gammopathy, is evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). However, PEP and IFE are not satisfactory in sensitivity, objectivity, and facility. Recently, a highly sensitive, automated immunoassay for measurement of free light chain (FLC) concentrations in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. To explore the clinical usefulness of measurement of FLC concentrations, we measured the kappa and lambda FLC concentrations and calculated the kappa/lambda FLC ratios for three groups [multiple myeloma (MM), other diseases, and control] and compared the results of the FLC assay with the results of PEP or IFE. The concentrations of serum kappa and lambda FLCs and the kappa/lambda FLC ratios for the MM group and non-MM groups were distinct. In the MM group, some sera and urine samples had no evidence of M protein on PEP and IFE, but FLC assay showed abnormal concentrations of FLCs and abnormal kappa/lambda FLC ratios in most cases. As compared with the PEP, the kappa/lambda FLC ratio revealed higher sensitivity in all diagnostic ranges with different cutoff values. Particularly, when the cutoff value 2.0 for kappa/lambda FLC ratio was used, specificity and positive predictive value were largely improved than when the cutoff values 1.2 and 1.5 were used. These findings indicated that FLC assay enables to detect myeloma patients with very low M protein due to early stage or after therapy and to distinguish patients with monoclonal increase of FLC from patients with polyclonal increase of FLC due to other conditions, particularly using kappa/lambda FLC ratio 0.3-2.0 as a diagnostic range. Despite some technical limitations of the assay, the incorporation of kappa/lambda FLC ratios with FLC concentrations is useful in the detection of M protein, particularly with negative serum or urine IFE results, and differentiation of monoclonal gammopathies from patients with polyclonal increase in FLC due to other conditions.

PURPOSE Heptaplatin (SKI-2053R, Sunpla ), a new platinum analogue which has a better toxicity profile than cisplatin, has been used with 5-fluorouracil (5-FU) continuous infusion for the treatment of advanced gastric carcinoma. However, continuous 5-FU infusion had a inconvenience to administration. The aim of this study was to evaluate the efficacy and toxicity of heptaplatin, UFT-E and leucovorin combination chemotherapy in advanced gastric cancer. MATERIALS AND METHODS A total of 22 patients was enrolled in this study at Kyung Hee University and Korea University from September 1999 to May 2001. Heptaplatin 400 mg/m2 was given as intravenous infusion for 1 hour at day 1. Oral UFT-E 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. RESULTS The 22 enrolled patients received 81 courses of chemotherapy and the median number of course per patient was three with a range of one to six. Five of 21 patients achieved partial responses (23.8%; 95% confidence interval, 5.6% to 42%) without complete response. Out of the 5 responding patients, three had unresectable perigastric lymph-nodes, one patient had a ovarian metastasis, and one patient had a peritoneal metastasis respectively. Main toxicities were neutropenia and nausea/vomiting. Grade 3 and 4 neutropenia were observed in 4 patients (18%) and grade 3 nausea/vomiting were observed in 5 patients (22.7%). The median time to progression was 4 months (range, 0.5 to 13 months), and median survival duration was 7.5 months (range, 2.0 to 14 months). Median response duration was 5.0 months (range, 1.5 to 10 months). CONCLUSION A combination chemotherapy of heptaplatin, UFT-E and leucovorin has a comparable efficacy with those of previously reported heptaplatin and intravenous regimen of 5-FU and controllable toxicity in advanced gastric carcinoma. Further study with large patient population is warranted to determine the usefulness of this regimen.

Azacitidine (AZA) is commonly used in patients with myelodysplastic syndrome (MDS). To determine the role of AZA before allogeneic stem cell transplantation (allo-SCT), we conducted a prospective study of AZA pre-treatment followed by allo-SCT in patients with higher-risk MDS. Twenty-one patients who were scheduled for their third to sixth cycle of AZA pre-treatment followed by allo-SCT were enrolled. AZA pre-treatment was interrupted early in 3 patients (14.3%) because of leukaemic transformation or death. The overall response rate to AZA pre-treatment was 57.1%. There were 2 cases of complete remission, 1 case of partial remission, and 9 cases of haematologic improvement. Fourteen patients (66.7%) received the planned allo-SCT and 5 patients were alive at the last follow-up. Three-year progression-free survival (PFS) and 3-year overall survival (OS) in the 14 patients who received allo-SCT were 30.0% (95% CI 3.3-56.7) and 42.9% (95% CI 17.1-68.7), respectively. PFS and OS were not influenced by response to AZA pre-treatment (p > 0.05). In this study, AZA had a role as a bridge therapy to prevent leukaemic transformation prior to selection of a donor for allo-SCT and showed low toxicity. It may be considered in patients with higher-risk MDS.

Lymphomatous involvement of the heart is extremely rare at initial diagnosis and presentation of malignant lymphoma. Worldwide, only a few cases have been diagnosed and treated during life and only four cases were diagnosed before death in Korea. We report a case of non-Hodgkin's lymphoma with two right atrial masses detected by chest computed tomography and transesophageal echocardiography. The patient was an 80 year- old man and the presenting symptoms included generalized weakness, weight loss, constipation and low abdominal pain. For diagnosis, the mass of the perinephric area was biopsied under ultrasonographic guidance, and pathologically it was determined to be malignant lymphoma, diffuse large B cell type. The patient was treated with continuous low dose cyclophosphamide and prednisolone vice standard chemotherapy because of advanced age and renal dysfunction. After 2 months of treatment the masses in the atrium and the intraabdominal masses disappeared.

Aim Although the etiology of plasma cell dyscrasia is poorly understood, there is evidence for immune dysregulation or sustained immune stimulation playing a pivotal role in the pathogenesis of these diseases, including chronic infection and autoimmune disorders. In this study, we report four autoimmune disease cases where monoclonal gammopathy (MG) was incidentally found during follow-up. Methods We retrospectively reviewed the medical charts and laboratory test results in the following four cases: neuromyelitis optica, Kikuchi disease, Sjogren syndrome and ankylosing spondylosis. Results The four patients were older than 55 years and the male-to-female ratio was 2 : 2. The autoimmune disease in each case developed differently because two patients had coincidental detection of MG, whereas MG was detected 2 years and 10 years after diagnosis in the other two patients. The amount of M-components in the blood for two cases was ≤ 1 g/dL. For the other two subjects, M-components were ≥ 3 g/dL. Conclusion A high prevalence of MG of undetermined significance (MGUS) has been noted in a series of patients with immune disorders, suggesting a possible association with MG. Further studies should focus on determining how MG relates to various clinical information and laboratory parameters, such as disease duration, disease activity and higher sedimentation rate. In the future, we also need to identify which stimuli, such as cytokine types and levels, can induce lymphocyte clonal transformation and the production of monoclonal antibodies.

BACKGROUND The spectrum of laboratory tests used to detect monoclonal components (M-components) include serum and urine protein electrophoresis (PEP), immunofixation electrophoresis, and immunonephelometric methods such as free light chain assay (sFLC). METHODS In this study, we retrospectively analyzed 78 patients who were to be tested with FLC without previous evidence of MG in order to investigate the clinical meaning of K/L screening. Abnormal K/L in sFLC was found in 25 samples from 21 patients (21/78, 26.92%). RESULTS Among them, serum electrophoresis was requested for 16 patients where 5 were diagnosed as either normal or polyclonal gammopathy, 5 as plasma cell myeloma, 5 as monoclonal gammopathy of undetermined significance and I as amyloidosis. In total, 11 patients were revealed to have MG related diseases (11/25, 44.0 %). CONCLUSIONS The clinical function of sFLC as a MG screening tool turned out to be effective based on the result where 16 out of 21 patients who were subject to further study led to diagnoses of MG related diseases in 11 patients. To provide an accurate evaluation for the performance of sFLC as a screening tool for MG, further studies should include additional confirmation of PEP results for patient groups that showed normal K/L ratios.

The present study sought to elucidate the role of induction and consolidation therapy in elderly patients. We retrospectively collected data of 477 patients who were aged over 60 years at the time of acute myeloid leukemia (AML) diagnosis. The median overall survival (OS) was 339 days in the induction group (n = 266) and 86 days in the best supportive care group (n = 211) (P0.001). In the induction group, the complete remission (CR) rate was 58.3 %, and treatment-related death was 15.4 %. Successful induction was related to good performance [Eastern Cooperative Oncology Group (ECOG2)] [hazard ratio (HR) 3.215; P = 0.002]. Mortality correlated with failure to achieve CR (HR 4.059; P0.001) and poor performance status (ECOG2) (HR 2.731; P = 0.035). In CR patients, poor karyotype and absence of consolidation (HR 2.313; P = 0.003) correlated with mortality. More than one cycle of consolidation was associated with better OS (P0.001). Lack of salvage therapy was associated with mortality in patients who did not achieve CR (HR 3.223; P = 0.005). Intensive induction in patients with good performance and1 cycle of consolidation after CR may be the best strategy for improving OS in elderly AML patients.

Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA).This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA.A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline.This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented.

To investigate how capillary electrophoresis (CE) works in oligo-secretory myeloma (OSM), we report a case here of OSM using multiple diagnostic methods including gel electrophoresis (GE), CE, and free light chain assay (sFLC). Also, we provide a brief review of laboratory methods to compare their diagnostic utilities in OSM.A 72 year-old Korean male suffering from low back pain during the past 6 months was transferred to the department of neurosurgery in order to evaluate abnormal findings in an imaging study, suggesting plasma cell myeloma (PCM) with multiple bone metastasis. CE showed no suspicious M-component; however, it showed increased Kappa components and skewing Kappa/Lambda ratio (K/L). Bone marrow examination revealed plasma cells observed up to 70%, which were compatible with sFLC results.Based on these results, the diagnosis turned out to be OSM with multiple bone metastases. Thereafter, the patient started the first cycle of chemotherapy accompanied by palliative radiation therapy.In our case, sFLC showed abnormal Kappa and K/L results from both serum and urine specimen. Therefore, it seems to be more sensitive and appropriate than both GE and CE to diagnose OSM.

Background To investigate how capillary electrophoresis (CE) works in oligo-secretory myeloma (OSM), we report a case here of OSM using multiple diagnostic methods including gel electrophoresis (GE), CE, and free light chain assay (sFLC). Also, we provide a brief review of laboratory methods to compare their diagnostic utilities in OSM. Methods A 72 year-old Korean male suffering from low back pain during the past 6 months was transferred to the department of neurosurgery in order to evaluate abnormal findings in an imaging study, suggesting plasma cell myeloma (PCM) with multiple bone metastasis. CE showed no suspicious M-component; however, it showed increased Kappa components and skewing Kappa/Lambda ratio (K/L). Bone marrow examination revealed plasma cells observed up to 70%, which were compatible with sFLC results. Results Based on these results, the diagnosis turned out to be OSM with multiple bone metastases. Thereafter, the patient started the first cycle of chemotherapy accompanied by palliative radiation therapy. Conclusions In our case, sFLC showed abnormal Kappa and K/L results from both serum and urine specimen. Therefore, it seems to be more sensitive and appropriate than both GE and CE to diagnose OSM.

Background: There has been increasing interest in the patients perspective on the outcome of the treatment. The Haemophilia Activity List (HAL) has been developed as a disease-specific questionnaire for haemophilia patients and is a validated self-report measure of function developed according to WHO International Classification of Functioning, Disability and Health. In this study, we performed a cross-cultural adaptation and linguistic validation of the HAL questionnaire to assess the health-related quality of life in Korean hemophilia patients in the future. Methods: To validate HAL in Korean, the English versions of HAL were translated into Korean using the forward-backward translation method and merged into a final Korean version. Validation was performed against the Korean version of the questionnaires EQ-5D-5L (EQ-5D) as general tool and Routine Assessment of Patient Index Data (RAPID3) as similar disease-specific tool. All processes were done with permission of the developer and according to WHO guidelines. Results: One hundred patients with severe and moderate forms of haemophilia A and B from Korea Hemophlia Foundation were invited to participate in the study. Spearmans rank correlation test was used for validation and internal consistency of the HAL was calculated with Cronbach alpha. Eighty-seven patients (87%) (18-62 years old) answered the questionnaires. The internal consistency of the Korean version of HAL was high, with Cronbachs alpha being 0.80-0.95. Upper extremity function had the highest consistency and leisure activities and sport had the lowest. The correlation was good between the HAL overall score and EQ-5D overall (r=0.78), EQ-5D usual activity (r=0.79), and RAPID3 physical function (r=0.82). Conclusion: The Korean version of HAL has reliability from internal consistency and intraclass correlation by test-retest analysis. The Korean version of HAL has validity which correlated with EQ-5D as general tool and RAPID3 as similar disease-specific tool. This questionnaire of Korean version can be useful as a hemophilia disease-specific instrument for evaluation of the health-related quality of life in Korean patients. Disclosures No relevant conflicts of interest to declare.

e20587Abstract Background: Neutrophil count is associated with prognosis in some cancers. Direct cell-cell interactions between neutrophils and tumor cells enhance tumor growth in Non-small cell lu...

The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS

Because plasma cell leukemia (PCL) is a rare and distinct variant among plasma cell dyscrasias, recent clinical and cytogenetic studies have been performed in different ethnic groups to define the characteristics of these PCL patients. As far as we know, IGH rearrangements involving t(11;14) and (14;16) are significantly more frequent in PCL than in myeloma patients. However, PCL cases associated with t(6;14)(p21;q32) or IGH-CCND3 rearrangement are extremely rare in the literature; only one PCL case with t(6;14) has been documented. A 61-year-old female was admitted due to fatigue, weight loss, and exertional dyspnea. Plasmacytoid cells were counted up to 76% at a peripheral blood film, but bone marrow aspiration failed because of dry-tapping. Flow cytometric analysis showed positive for CD138 and cytoplasmic kappa light chain. Chromosome analysis revealed t(6;14)(p21;q32), which was confirmed by an IGH split-out probe in FISH analysis. Immunofixation electrophoresis also presented monoclonal bands identified as IgG and kappa light chain. Finally, she was diagnosed as primary PCL associated with t(6;14) and IGH rearrangement. Although considerable advances have been made in the understanding of the biology and molecular pathogenesis of PCL, further clinical, laboratory, and genetic studies of PCL associated with such a rare IGH rearrangement would be necessary in the future. To the best of our knowledge, this is the first report of PCL associated with t(6;14) as a sole chromosomal abnormality.