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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.

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.

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.

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 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.

Recent rapid developments in new technology such as whole genome/exome sequencing have revealed that novel mutations in genes such as DNMT3A , IDH1 , IDH2 and TET2 contribute to the main process of leukemogenesis in patients with normal karyotype acute myeloid leukemia (AML).[1][1] Among these genes

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.

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.

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.

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

Background Familial form of acute myeloid leukemia (AML) is not well known except for extreme cases. BRCA1/2 and p53 germline mutation are well known genetic changes that is related to familial AML¡¯s. Because of diverse penetrance potential of germline mutations and complex pathogenesis for the development of AML, it is not easy to discern familial form of AML. In this study, we performed next generation sequencing (NGS) study of a family who has been suspected to have familial form of AML. Material and method Two relatively young patients have been referred to our institution for AML. One was a 41 years old male (son) and the other was 58 years old female (mother). To discover genetic factors involved in hematological familial cancer syndrome, we performed WGS/WTS using DNA of mother and son who are AML patients and WGS using DNA of healthy father. Tumor DNA and RNA of mother and son were extracted from bone marrow samples which were collected at the time of diagnosis and control DNA and RNA was extracted from saliva and bone marrow samples, respectively, at the time of CR. WGS were performed using HiSeq X ten (illumina, San Diego, USA). For WTS, we used HiSeq2000 platform (illumina, San Diego, USA). For the analysis of WGS, we used GATK unifiedGenotyper for caller in this study. The first filter was set an average depth >10 and conf_cut > 50. And next filter step was using several databases (dbSNP, clinvar, cosmnic70, nci60) and filtering tools (Meta SVM and Meta LR) to filter out of called loci. Meerkat was used to analyze structure variations (SVs). To analyze DEGs using WTS, we used HTSeq-count. To analyze DEGs, we used WTS and HTSeq-count. Results and discussion A total of 3,695,266 loci of normal DNA and 3,977,321 loci of tumor DNA were found in mom samples and 3,622,083 of these were commonly found in both normal and tumor samples. Similarly, a total of 3,513,806 loci of normal and 3,935,873 loci of tumor DNA were found in son samples, of which 3,476,405 were commonly found. Of these common loci, we identified 2,799,429 that are universally present in both mum and son. To determine genes that are found only in patients (Mon and son), we filtered out the loci of father¡¯s SNPs and excluded 2,191,882 loci We subsequently identified a total of 607,547 candidate loci which have association with AML malignancies. Using Support vector machines (SVMs) and DNM filter, we found 37 significant genes that are considered to be related with de-novo AML Among these, 12 were (AGL, COL12A1, IMPDH1, LIPN, MET, MYH13, PBX3, ROBO3, SLC34A3, SMO, THBS1 and TP63) already reported to have an association with hematopoietic disorder, while 25 were a novel mutation genes. The most interesting gene is THBS1. It is reported to affect hematopoietic differentiation function via CD36 and CD47 and a greater than 3 fold change was found in both mum and son in DEG analysis. In DEG analysis, total 1317 gene in mother and 473 genes in son were shown differently expressed above 3FC. The number of recurrent DEGs between mother and son is 144 and these genes were estimated to involve in Systemic lupus erythematosus, Chemokine signaling and bladder cancer pathway. We used Mutect to detect somatic mutation that acts as second hit. 29 nonsynonymous-SNVs were detected in son sample and 43 nonsynonymous-SNVs were detected in mother sample. OR11H1 gene was recurrently shown in both mother and son. We performed Structure variants analysis to identify second hit SVs using Meerkat in mother and son separately SVs of mother were detected in several regions and 69 genes were detected in exonic regions, 39 genes were somatic SVs and 12 of these were filtered out because the genes were also detected in the normal sample of son. 27 SVs genes are considered as a candidate of AML second hit in mother. On the other hand, we found 5 genes somatic SVs in son using the same method. Of note, FAM231A gene overlapped with mom tumor sample and son tumor sample. In conclusion, we found 37 significant genes may be related with de-novo AML. In addition, several genetic factors affect tumorigenesis through second hit. Figure 1. Association between THBS1 and other genes by gene to gene networking Figure 1. Association between THBS1 and other genes by gene to gene networking Figure 2. Expression level and heatmap of gene expression of mother and son by DEGs analysis Figure 2. Expression level and heatmap of gene expression of mother and son by DEGs analysis Figure 3. Circosplot of Structure Variantions(SVs) of mother and son Figure 3. Circosplot of Structure Variantions(SVs) of mother and son Disclosures No relevant conflicts of interest to declare.

Various factors released from BMSCs regulate the biologic behaviors of AML cells involving in responsiveness of chemotherapeutic treatment. Cytotoxic effect of Ara-C decreased when AML cells co-cultured with BMSCs. IL-6 expression was prominently increased when HEL cells were co-cultured with BMSCs. Even though IL-6 did not affect the growth of HEL cells, Ara-c mediated apoptosis was suppressed by BMSCs. Also, IL-6 induced the phosphorylation of AKT and its downstream gene (mTOR). Ara-C mediated H2AX mRNA was suppressed when Ara-C was treated with co-cultured HEL cells with BMSCs. Also, its expression was down-regulated in HEL cells co-treated with Ara-C plus 25 nM IL-6. Prevention of IL-6 mediated signaling by gp130 shDNA slightly suppressed Ara-C induced H2AX expression when gp130 shDNA transfected HEL cells were co-cultured with BMSCs under 10-6 M Ara-C treatment. In vivo model, we found that IL-6 expression levels in serum of mice detecting AML cells following Ara-C treatment were higher than in serum of mice not detecting residual AML cells. Even though somatic mutation of gp130 gene was not detected in the genome analysis of AML, the overall survival was statistically different depending on the IL-6 levels in serum of bone marrow. Our findings suggest that IL-6 releasing from BMSCs help AML cells to survive against Ara-C treatment resulting in developing relapase from enhancing the growth of minimal residual cells. Figure 1. IL-6 suppresses Ara-C mediated apoptosis of HEL in vitro assay. Figure 1. IL-6 suppresses Ara-C mediated apoptosis of HEL in vitro assay. Figure 2. IL-6 suppresses Ara-C mediated H2AX expression in HEL cells. Figure 2. IL-6 suppresses Ara-C mediated H2AX expression in HEL cells. Figure 3. Survival curve depending on IL-6 level of AML patients bone marrow serum. Figure 3. Survival curve depending on IL-6 level of AML patients bone marrow serum. Disclosures No relevant conflicts of interest to declare.

Background The long-term outcomes of adult patients with immune thrombocytopenic purpura (ITP) after splenectomy are not clear. Methods We retrospectively analyzed 31 patients who underwent splenectomy after diagnosis of ITP at our institution between 1990 and 2009. Long-term follow-up was defined as a follow-up that lasted 1 year or more from splenectomy to the last follow-up. Results The overall response rate to splenectomy was 84%. However, the response rate at 6 and 12 months decreased to 77% and 68%, respectively. During the 6 years of median follow-up after splenectomy, 11 patients (35%) relapsed. The long-term response rate was 55%. The long-term follow-up of 26 patients after responding to splenectomy showed that the median time from splenectomy to relapse was 19 months in the partial response (PR) group; however, there was no relapse after 9 months in the complete response (CR) group. Variables, including age, were not predictive of the long-term response after splenectomy. Additional treatment in patients who did not respond or relapsed after splenectomy was mostly effective. After a median follow-up of 7 years (range: 1-25 years) from the diagnosis, there were 2 deaths, including one due to spontaneous bleeding after repair of duodenal ulcer perforation. Conclusion Although splenectomy is safe and effective, the response rate after splenectomy continuously decreases over time. The duration of response is different between the patients that achieved CR and those that achieved PR. Factors, including age, were not predictors of a response to splenectomy.

More than a half of anaplastic large cell lymphoma (ALCL) harbors an aberrant NPM-ALK fusion gene, which activates a number of down-stream signaling pathways such as Ras/ERK, PI3K/AKT, and JAK3/STAT3. Through this mechanism, mTOR pathway is also activated in ALK-positive ALCL (Vega F, et al. Cancer Res 2006). Everolimus, an mTOR inhibitor, has shown promising anti-tumor activity in a variety of lymphomas (Jundt F, et al. Blood 2005; Wanner K, et al. Br J Haematol 2006; Haritunians T, et al. Leukemia 2007), although the clinical efficacy of everolimus monotherapy was not satisfactory, possibly due to activation of several pro-surviving signaling pathways. The combined effect of everolimus and crizotinib, an ALK inhibitor, has not yet been investigated in ALK-positive tumors so far. The aim of this study was to evaluate the effect of everolimus in combination with crizotinib in ALK-positive ALCL cell lines, K-299 and SU-DHL-1. We treated K-299 and SU-DHL-1 cells with various concentrations of everolimus and crizotinib at a fixed ratio of 1:40 (Figure 1). After 72 hours, the combination index (CI) values calculated by the Chou-Talalay method were less than 1 (range, 0.583-0.763 in K-299 cells and 0.271-0.616 in SU-DHL-1 cells) in all tested combinations, suggesting synergistic cytotoxicity of everolimus and crizotinib. The Western blot analysis (Figure 2) demonstrated that everolimus treatment up-regulated the phosphorylation of ERK Thr202/Tyr204 and AKT Thr308 and Ser473 in K-299 cells. However, this aberrant activation of ERK and AKT was attenuated by the addition of crizotinib. In addition, while everolimus selectively inhibited phosphorylation of mTOR Ser2448, a marker for mTORC1 activity, the combination treatment more potently inhibited mTOR Ser2448 phosphorylation and decreased phosphorylated mTOR at Ser2481, a marker for mTORC2, as well. In the cell-cycle analysis, the combination treatment induced G1 arrest. Everolimus treatment alone did not increase the fraction of cells in the sub-G1 region compared to the control (2.16% vs. 4.03% in K-299 and 1.34% vs. 1.68% in SU-DHL-1), while crizotinib monotherapy increased the sub-G1 population (11.88% vs. 4.03% in K-299 and 28.68% vs. 1.68% in SU-DHL-1). The combination of crizotinib and everolimus markedly increased the sub-G1 population in both ALK-positive ALCL cell lines (22.25% in K-299 and 46.40% in SU-DHL-1). PARP cleavage was also increased after the combination treatment. To test the hypothesis that our findings could be applyed to other ALK-positive malignancies, we treated NCI-H2228, a lung adenocarcinoma cell line that harbors an EML4-ALK fusion gene, with everolimus and crizotinib for 72 hours. The CI values were less than 1 in all tested combinations: 0.228 in 1 nM everolimus plus 80 nM crizotinib, 0.216 in 2 nM everolimus plus 160 nM crizotinib, and 0.349 in 4 nM everolimus and 320 nM crizotinib. In summary, everolimus combined with crizotinib synergistically inhibited the growth of ALK-positive ALCL cells. Crizotinib abrogated aberrant ERK and AKT signaling activation induced by everolimus and more potently inhibited both mTORC1 and mTORC2 activity when combined with everolimus, resulting in increased G1 cell-cycle arrest and apoptosis (Figure 3). Our findings may provide an evidence for future research using everolimus and crizotinib combination in ALK-positive ALCL and could be used to improve the therapeutic outcome in patients with ALK-positive ALCL. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Purpose According to our experience, ethnic difference in acute myeloid leukemia (AML) is considerable, especially between Caucasians and Asians. In this study, first we tried to identify genomic signature of Korean AML patients and investigat how these genomic signatures would correlate with clinical parameters. Additionally, we tried to compare genomic signatures of Korean AML patients with that of TCGA. Methods We identified specific single nucleotide variant (SNV)'s, small indels and copy number variation (CNV)'s using whole exome sequencing (WES) of acute myeloid leukemia (AML) samples from 103 patients. For detection of SNV's and small indels, we used in-house algorithm Adiscan (https//www.syntekabio.com). For detection of CNV's, we used CONTRA. Clinical parameters considered includes gender, age, bone marrow blast percentage, WBC count at diagnosis, French-American-British (FAB) classification, WHO classification, disease free survival (DFS), reception of allogeneic stem cell transplantation (ASCT) and overall survival (OS). We used TCGA data available on cBio portal. Results In the analysis, when clustering analysis was performed, gender did not have correlation with genetic signatures both in terms of SNV's, indels and CNV. For patient's age, genetic signature of middle-aged patients (age between 35-60) was rather diverse compared to the young patients (age 60). From phenotypical perspective, M4 and M5 AML by FAB had common genetic signatures, which was in contrast to M2 and M3 disease. It is of note that M3 disease does have heterogeneous genetic signature. When the prognosis of AML patients were considered, patients with excellent prognosis (complete remission for more than 3 years) had rather homogenous genetic clustering, while patients with poor prognosis (relapse in 1 year) had very heterogeneous genetic clustering, which implicate complexity of disease relapse mechanism. Commonly mutated non-synonymous genes include TPMRSS13, IDH2, TTN, TNN, NXPE1, NRAS, FAT1, DNMT3A, ANO1, and ADAMTS15. Copy number changes were observed in genes including PTPRC, PTPRQ, NBR1, and WASL. TPMRSS mutation seemed to have prognostic value but further validation is necessary. Compared to TCGA, TMPRSS13 mutation and TNN mutation were unique SNVs found in Korean AML. On the other hand, frequency of IDH2, NRAS, and DNMT3A was considerably low in Korean AML patients. Conclusion Korean AML patients have their own genetic signature which is distinct to that of Caucasians, which supports ethnic difference of AML. TMPRSS13 and TNN mutation in Korean AML patients are noticeable. Figure 1 Commonly found SNV's found by WES in Korean AML patients and its relation with clinical parameters Figure 1. Commonly found SNV's found by WES in Korean AML patients and its relation with clinical parameters Figure 2 Commonly found CNV's found by WES in Korean AML patients and its relation with clinical parameters Figure 2. Commonly found CNV's found by WES in Korean AML patients and its relation with clinical parameters Disclosures No relevant conflicts of interest to declare.

Background Acute promyelocytic leukemia (APL) has the best prognosis among acute myeloid leukemia (AML). However, a subset of APL patients is not cured with all-trans retinoic acid (ATRA) combined with anthracycline-based cytotoxic chemotherapy. Some mechanisms such as increased ATRA metabolism have been suggested to acquired resistance to ATRA. However genetic mechanism of ATRA resistance has not been characterized at all. Hence, in this study, we tried to reveal genetic alterations attributable to ATRA resistance. Methods First, we performed whole exome sequencing (WES) using DNA of three APL patients who showed resistance to ATRA based treatment. These included two patients who failed to achieve complete remission (CR) after induction chemotherapy, and one patient who experienced relapse after CR despite of consolidation treatment. DNA extracted from bone marrow at the time of diagnosis was used for analysis, while DNA extracted from saliva at the time of CR was used as germline control. Calling of single nucleotide variants (SNV) was performed using internal pipeline called Adiscan (http://www.syntekabio.com). Annotation was performed using Polyphen-2. SNV’s found by WES were validated by direct Sanger sequencing. The frequency of those validated SNV’s was defined in a separate APL cohort. Results We identified 34 somatic non-synonymous SNV’s in three patients. Polyphen-2 algorithm predicted 9 among 34 SNV’s to damage protein function. Sanger sequencing revealed 8 over 9 SNV’s to be validated. These validated SNV’s include RXRG M77R, N6AMT2 A78S, TXNDC15 D198E, B3GALTL A444T, RBBP8NL E182G, TNPO3 L173W, BHMT M185I and ADAMTS5 G85D. When these 8 SNV’s were genotyped in a separate cohort, none of these SNV’s was found in the APL cohort composed of 30 ATRA sensitive patients, suggesting these SNV’s would be truly related to ATRA resistance in APL. Especially, when a simulation using amber molecular dynamics was performed, we observed 1) Increase in hydrogen bonding, 2) Decreased helix folding structure, 3) Decreased energy state in RXRG mutant case. Conclusions WES identified eight SNV’s which were unique in ATRA resistant cases. Among those mutations, RXRG could be a promising nonsynonymous mutation that explains the genetic mechanism of ATRA resistance. Disclosures No relevant conflicts of interest to declare.

Background: Uncontrolled complement activation has a major role in the pathogenesis of atypical HUS (aHUS) and the restraint of this process by eculizumab is life saving. However, the evidence of complement dysregulation in the pathogenesis of Thrombotic Thrombocytopenic Purpura (TTP) is still unclear. In this study we examined the presence of complement activation biomarkers in patients with aHUS and TTP and the levels were compared to normal healthy controls . Patients and Methods: Patients with thrombotic microangiopathic thrombocytopenia diagnosed either as TTP with low ADAMTS13 activity less than 10% or aHUS with impaired renal function, Cr> 2mg/dL and normal ADAMTS13 activity were chosen from the Korean TTP registry from February 2012 to June 2014. Prospective plasma and serum samples prior to intervention were collected from newly diagnosed patients with TTP (n=20), aHUS (n=20), and 20 healthy controls and frozen at -700C. Complement activation products (C3a, Bb as alternative pathway; C4d as classic pathway; C5a, C5b-9; terminal pathway) were measured by ELISA. Results: Significantly increased levels of Bb and C5b-9 were observed in TTP (median [range], ng/mL; Bb, 1220 [540.0 – 16560], p=0.048; C5b - 9, 390.1 [238.5 - 938.7], p Conclusion: Complement biomarkers are activated to a similar level in both newly diagnosed cases of TTP and aHUS. Complement activation product levels did not differentiate aHUS from TTP. Disclosures No relevant conflicts of interest to declare.

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.

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count (500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.

Dear Editor, Multiple myeloma, a hematologic malignancy characterized by the proliferation of a neoplastic plasma cell clone in the bone marrow, accounts for 10% of hematologic malignancies [1]. The common presenting features, such as anemia, bone pain, hypercalcemia, and increasing susceptibility to infections, are caused by the infiltration of plasma cells and changes in plasma protein [2]. Large amounts of monoclonal protein and a loss of functional antibody production can cause immunological dysfunction and distinct laboratory findings. In multiple myeloma, an ABO discrepancy can result from protein abnormalities causing rouleaux formation or pseudoagglutination in the blood group test [3]. Here, we report a novel case of ABO discrepancy in a patient with IgA kappatype multiple myeloma caused by the loss of isoagglutinin. A 78-year-old woman who had been suffering from multiple myeloma (IgA, kappa type) for 8 years was admitted for a scheduled chemotherapy. The total protein (9.6 g/dl) was elevated due to a large amount of IgA (4,430 mg/dl), whereas, the levels of uninvolved immunoglobulins were reduced (IgG, 236 mg/dl and IgM

To establish patient-derived multiple myeloma (MM) cell lines, mononuclear cells obtained from a MM patient’s bone marrow were directly injected via tail vein into a NRG/SCID mouse. Fourteen weeks after injection, tumor developed at subcutis and bone marrow (BM) in the same mouse. We separated and cultured cells from these two sites (subcutis and BM) and established two cell lines originating from a single patient (SNU_MM1393_BM and SNU_MM1393_SC). In cytogenetic analysis, karyotype of newly established two MM cell lines showed tetraploidy which is different from the karyotype of the patient (diploidy) indicating clonal evolution. In FACS analysis, the expression of CD138 and CD45 was detected in both cell lines. Response to IL-6 and soluble IL-6 receptor was different between the two cell lines. Moreover, SNU_MM1393_SC showed higher degree of resistance against proteasome inhibitor (bortezomib) compared to SNU_MM1393_BM. However, two cell lines were both sensitive to histone deacetylase inhibitor (panobinostat). When whole exome sequencing was performed using the DNA of these two cell lines, a set of somatic mutations involving Wnt signaling and NF-kB pathway were detected in both cell lines. Additional somatic mutations of JAK1, PLCG1, IRS2, and HGS which are known to interact with JAK/STAT pathway were detected in SNU_MM1393_BM. Whereas, additional somatic mutations of EGFR, HSP90AB1, CFDR, and CALML5, which are known to interact with growth factor cell signaling pathway were detected in SNU_MM1393_SC. These findings highlight the importance of interactions between tumor and tumor microenvironment as the myeloma progresses and will pave a way to more effective selection of targeted agents according to specific tumor characteristics obtained in the process of disease progression. Disclosures: No relevant conflicts of interest to declare.

Abstract 2188 The clinical utility of ADAMTS13 activity for TTP has been extensively studied for last years. However, the clinical significance of ADAMTS13 activity for response to treatment, mortality rate, recurrence, and prognosis is still unclear. We previously reported the characteristics of severe ADAMTS13 deficiency in thrombotic thrombocytopenic purpura (TTP) and patients with severe ADAMTS13 deficiency had lower serum creatinine levels than patients with non-severe ADAMTS13 deficiency using 66 patients enrolled from January 2005 to December 2008. (Jang MJ et al, Int J Hematol 2011;93:163–9). In this second report, we enrolled 65 additional patients from January 2009 to June 2012 and analyzed 131 TTP patients using same methods. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels (P=0.001), lower platelet counts (P Disclosures: No relevant conflicts of interest to declare.

Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.

Abstract 1990 Introduction: Autologous stem cell transplantation (ASCT) is a standard of care for younger multiple myeloma patients (pts). However, nearly all pts undergoing ASCT will relapse and require salvage therapy. Several investigators have reported 2nd ASCT might be a feasible and effective treatment modality in some pts. However, these studies contained small number of pts with 2nd ASCT and did not compare with outcomes of salvage therapy using novel agents. Thus, the aims of this study are to investigate outcomes of 2nd ASCT in pts relapsed after front-line ASCT and identify the impact of 2nd ASCT compared to modern systemic therapy in the novel agent era. To minimize the heterogeneity between the 2 groups, matched-pair design was chosen. Methods: The data of 48 pts between 1998 and 2010 with 2nd ASCT after relapse of front-line ASCT identified from web-based registry (www.myeloma.or.kr) were analyzed. Pts with tandem ASCT or salvage allo-SCT were excluded. The goal of this study was to perform a matched-pair analysis, each patient with 2nd ASCT was matched to three pts from a cohort of 517 pts treated with systemic chemotherapy after relapse of prior ASCT. The pts were matched for 9 potential prognostic factors: age at relapse (MEL140), response to front-line ASCT (≥VGPR vs Results: The median age at relapse was 55.5 (range, 33.4–68.5) years and 106 pts (55%) were male. The ISS was I(54, 28%)/II(84, 44%)/III(54, 28%). Serum LDH level was elevated in 133 (69%) and sCr ≥2mg/dL was in 35 (18%). The data of conventional cytogenetic analysis was available in 156 pts (79%). Thirty-three (21%) were abnormal. Of these, 26 pts (79%) had complex chromosomal abnormalities, 15 (45%) del(13q), and 6 (18%) hypodiploidy. One hundred sixty (83%) received VAD as induction therapy for first ASCT. Conditioning regimen for first ASCT was MEL 140–200 mg/m2 in 187 (97%). Fifty-six (29%) received maintenance therapy after first ASCT. Response to front-line ASCT was 67 CR (35%), 39 VGPR (20%), 68 PR (35%), 13 MR/SD (7%), 5 PD (3%). The median TTP after first ASCT was 12.0 (range, 1.1–83.8) months, and pts with ≥18 months of TTP after first ASCT were 57 (30%). After matching process, we identified it was successful because the distribution of 9 matching variables and unmatched other variables (ECOG performance status, hypercalcemia, bone lesions) was balanced between 2 groups. 2nd ASCT conditioning consisted of MEL alone in 45 (94%), the remaining 3 had MEL with busulfan or bortezomib. Only one transplant-related death occurred following 2nd ASCT. Novel agents used as salvage therapy in their course of disease were bortezomib in 151 (79%), thalidomide in 138 (72%), and lenalidomide in 6 (3%). Thalidomide was less frequently used in the 2nd ASCT group than the systemic chemotherapy group (58% vs 80%, p=0.016). With a median follow-up of 55.3 (range, 3.4–140.0) months, the 2nd ASCT group revealed significantly better progression-free survival (median, 18.0 [95% CI, 15.2–20.8] months vs 9.1 [6.7-11.5] months, p=0.017, respectively) and overall survival (OS; median, 55.5 [46.2-64.8] months vs 25.4 [16.7-34.1] months, p=0.035, respectively) than the systemic chemotherapy group. In multivariate analysis for OS, Conclusion: The outcomes of salvage 2nd ASCT appear superior to those of systemic chemotherapy, even fewer pts in the 2nd ASCT group received thalidomide. Additionally, 2nd ASCT was an independent prognostic factor for better OS. Considering current low mortality of 2nd ASCT, our results might provide a substantial evidence for performing 2nd ASCT in relapsed myeloma pts and suggest the value of performing a prospective randomized trial comparing 2nd ASCT and systemic chemotherapy in pts relapsed after front-line ASCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 4812 Erythroid precursors proliferate, differentiate, and enucleate in the bone marrow niches called erythroblastic islands in contact with macrophages. However, the cell-to-cell communication between erythroblasts which are undergoing terminal maturation leading to enucleation is not well known. Moreover, the cell-to-cell interaction at a terminal erythroblast maturation stage was hardly detected in conventional suspension culture systems due to cell surface characteristics of electrostatic repulsion. To elucidate the communication between late maturing erythroblasts, erythroid cells, which were derived from human CD34+ cells, were cultured at conventional or supra-optimal densities. Surprisingly, the final yields of red blood cells (RBCs) were significantly increased in supra-optimal culture density, even in the absence of feeder stromal cells and serum or plasma. Also observed were increases in the rates of cell survival, expansion, and enucleation. Contact between cells observed in these supra-optimal cultures was associated with increases in adhesion-related signaling proteins (150 kDa and 123 kDa), the latter of which was previously unknown to be involved in erythropoiesis. The cultured erythroid cells showed erythropoiesis specific markers such as CD71, GPA, GATA-1 and b-globin. Therefore, we firstly elucidated that the erythroid cells which were in the final maturation step can communicate each other and affect their survival and maturation including enucleation without the help of macrophages. Also, the increased attachments between erythroid cells evoked adhesion-related signals. We anticipate that the culture of these cells at supra-optimal density may enhance in vitro RBC production for human transfusion. Disclosures: No relevant conflicts of interest to declare.

Abstract 3424 Patients with aplastic anemia (AA) are suffered from various complications related to bone marrow failure and peripheral cytopenia. Although immunosuppressive therapy or hematopoietic stem cell transplantation has been performed for curative purpose, the majority of patients have been treated only by supportive cares including repeated transfusion. However, because continued transfusion eventually induces iron overload in many tissues and organs, transfusional iron overload and its consequences are another life-threatening problems for AA patients. Previous reports about iron chelation therapy (ICT) have mainly shown its efficiency for decreasing tissue iron and safety. However, improvement in hematopoiesis after iron chelation therapy has been limitedly reported as case reports or trials involving small number of patients without objective tools for measuring tissue iron content. In the KAMS0112 study (a multi-center, open label, prospective study evaluating the efficacy of ICT with deferasirox in transfusional iron overload with myelodysplastic syndrome or AA using quantitative R2-MRI, Ferriscan), a total of 54 patients with AA showing serum ferritin level over 1,000 ng/ml were enrolled from 19 institutes, and further analyzed for the changes in hemogram during ICT as well as efficacy and safely of deferasirox. During the study, the specific treatments for AA, such as immunosuppressive therapy or hematopoietic stem cells transplantation, were not undertaken. During 1 year prior to study, patients received 23.7±16.9 units of red blood cell (RBC) product, and the baseline serum ferritin level and liver iron content (LIC) were 4,164±447 ng/ml and 20.1±12.0 mg Fe/g DW, respectively. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin level falls below 500 ng/ml, treatment was withheld. In spite of continued transfusional support during the study, serum ferritin level and LIC were significantly decreased after 1 year of ICT with deferasirox (Ds-ferritin=−3,076.7±489.9 ng/ml, p=0.0003; DLIC=−7.73 mg/Fe/g DW, p=0.001). To evaluate the improvement of each parameter in hemogram by ICT, patients with baseline hemoglobin level less than 8.0 g/dl (n=28), with baseline WBC count less than 4/ml (n=43), and with baseline platelet count less than 20/ml (n=31) were selected separately. At the end of study, hemoglobin level and platelet count (8.2±3.0 g/dl and 22.2±31.4/ml, respectively) was significantly increased from the baseline value (6.1±1.1 g/dl, p=0.001; 12.5±12.4/ml, p=0.05, respectively). WBC count was also slightly increased (from 2.1±0.9/ml to 2.3±0.9/ml, p=0.457). Considering the relatively uniform criteria of transfusion, the finding that hemoglobin level and platelet count could increase above 8 g/dl and 20/ml, respectively, after 1 year of deferasirox treatment is clinically significantly. Due to gradual improvement of anemia, requirement of RBC transfusion had continuously decreased during the study period (R2=0.31). This subanalysis of KAMS0112 study demonstrates that ICT using deferasirox can be effective in improving anemia and thrombocytopenia in the transfusional iron overload patients with AA, as well as reducing serum ferritin level and LIC. Further studies might be required to elucidate the mechanism involved in the improvement of hematopoiesis associated with correction of deranged intracellular iron homeostasis. Disclosures: Min: Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Lee:Novartis: Research Funding. Won:Novartis: Research Funding. Shim:Novartis: Research Funding. Kim:Novartis: Research Funding. Seung:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Chung:Novartis: Research Funding. Hyun:Novartis: Research Funding. Jo:Novartis: Research Funding. Jung:Novartis: Research Funding. Sohn:Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Joo:Novartis: Research Funding. Cheong:Novartis: Research Funding.

Abstract 4765 Purpose: Infection is the most important cause of death in immunosuppressed cancer patients. And the urinary tract is a common source of infection in children. So we investigated the frequency of urinary tract infection (UTI) and the treatment outcome in children with cancer who were receiving antineoplastic therapy. Methods: We reviewed the medical records of children who were diagnosed as UTI during chemotherapy because of hematologic malignancies or solid tumors from January 2003 to July 2010 in Kyungpook National University Hospital. We defined as UTI when the patient showed high fever over 38.5°C and the single bacterial organism was cultured over 10,000/mL in urine sample using midstream urine collection technique. The bacterial strain, duration of fever, laboratory tests including urinalysis and gram stain, and imaging studies were demonstrated. Results: There were 63 cancer patients (male:female = 39:24) and 47 of them (74.6%, male:female = 30:17) experienced UTI during chemotherapy at least once. No one showed urinary symptom/sign like dysuria, frequency, urgency, flank pain or costo-vertebral angle tenderenss. The total episodes of UTI were 133 (male:female = 96:37) and the number of infection was mean 2.8 (1~10) per one patient. The common organism was Escherichia coli (25.6%), Enterococcus faecalis (15.0%), Klebsiella pneumoniae (10.5%), Enterococcus faecium (6.8%), Proteus mirabilis (6.8%) and Stenotrophomonas maltophilia (5.3%). Initial urinalysis was performed in 115 cases, but only 4 of them (3.5%) revealed pyuria. All gram stain results were negative. Duration of fever was mean 2.1 (1~6) days. The initial absolute neutrophil count (ANC) was average 1,930/μ L (0 ~ 12,610/μ L). The renal cortex scan using dimercaptosuccinic acid was performed for 43 cases to verify pyelonephritis. One showed decreased tracer uptake of upper pole of right kidney, and another 3 revealed diffuse decreased tracer uptake in both kidneys without specific photon defect. One episode of 3 was considered as urosepsis because the same organism (Klebsiella pneumoniae) was cultured from not only urine but also blood. The patient revealed hypotension and decreased renal function (glomerular filtration rate 41.4 mL/min). No mortality was observed. Conclusion: UTI is a very common infection in immunocompromised cancer children regardless of ANC which showed excellent prognosis with broad spectrum antibiotics. The bacterial strain was not different from that of immunocompetent children. But their symptom/sign was silent and the initial urinalysis and gram stain were not much help. So it is important to check urine culture for febrile cancer children under chemotherapy although the complication is very rare after UTI. Disclosures: No relevant conflicts of interest to declare.

Abstract 1125 Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 97 patients with de novo MDS (n = 44) or idiopathic AA (n = 53) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a mean of 28.6 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (8.3%), 25 (69.4%), and 4 cases (11.1%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64.2%) were severe form. Mean value of serum ferritin level in enrolled patients was 3,482.6±436.7 ng/ml in MDS, and 3,904.4±399.2 ng/ml in AA at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 20.8 ± 3.5 mg Fe/g dry weight in MDS and 22.6 ± 2.2 mg Fe/g dry weight in AA. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p Disclosures: No relevant conflicts of interest to declare.

Abstract 4881 Introduction The Korean Multiple Myeloma Working Party (KMMWP) initiated a nationwide registration of myeloma patients via a web page designated the “Korean Myeloma Registry.” This registry includes demographic features, characteristics of disease, treatment outcomes, and survival status. Herein, we retrospectively reviewed data representing 3,209 Korean myeloma patients. Methods Members of the registry committee of the KMMWP designed the web-based registration site for the “Korean Myeloma Registry (www.myeloma.or.kr).” A total of 3,209 patients were registered from 39 hospitals. Each one of participated hospitals registered their patients who were diagnosed as MM between the years 1999 and 2009. The approximate duration of registration was from May 2005 until March 2009; following collection, the data was downloaded for analysis. Results The median age at diagnosis was 64 years (range, 20 – 93 years) with 84 patients ' 40 years of age; this included three patients < 30 years of age (ages 20, 28, and 29 years old). Poor performance status (ECOG grade 2-3), anemia (Hgb < 10 g/dL), hypoalbuminemia (< 3.5 g/dL), and elevated serum β2 microglobulin (> 5.5 mg/dL) were more frequently observed in the > 65 years of age group than in the groups '65 years of age. Thus, an advanced ISS stage was more common in patients older than 65 years. The most common idiotype of myeloma was IgG (46.0%, 1475/3209), followed by IgA type (18.6%). Non-secretory myeloma accounted for 4.4% of cases, with IgD, IgM, and IgE subtypes being very rare. However, patients ' 40 years of age demonstrated a tendency toward a higher incidence of the IgD type (7.1%, 6/84) and light chain disease (22.6%, 19/84) compared to the other age groups. Other characteristics, including the presence of extramedullary plasmacytoma, demonstrated a similar pattern among the groups. Chromosomal studies of bone marrow aspirates were performed in 1,943 patients with 499 patients (25.7%) demonstrating abnormalities. In 60.9% of patients (1,954/3,209), an objective response to induction treatment included complete response (CR), partial response (PR), and minimal response (MR) (Table 4); 463 patients demonstrated progressive disease (PD) during induction treatment. Response could not be evaluated in 300 patients (9.3%) due to early drop out, including follow-up loss and early death. Eight hundred four patients (25.1%) received SCT. The majority of patients (23.1%, 741 patients) received autologous SCT within one year of diagnosis; designated as “early transplantation.” Autologous SCT was performed in those patients who achieved an objective response following induction treatment. Sixty three patients (2.0%) underwent autologous SCT after relapse; designated as “delayed transplantation.” Five hundred eighty patients received single autologous SCT. Tandem autologous SCT was performed in 134 patients. Allogeneic SCT was performed for 63 patients following autologous SCT. The median OS was 50.13 months (95% confidence interval (CI) of 46.20 – 54.06 months). When OS was compared according to age strata, patients '40 years of age demonstrated a prolonged OS (median OS of 71.13 months) compared with patients > 65 years of age (median OS of 36.73 months, P < 0.001). When we compared the survival of patients who received novel agents such as bortezomib or thalidomide at any time during the course of their treatments with patients who did not receive novel agents, there was a significant difference of OS between two groups (median OS 42.23 versus 55.50 months, P < 0.001). Tandem autologous SCT produced a superior OS when compared with single autologous SCT. Furthermore, patients who underwent delayed SCT demonstrated a longer OS compared with early SCT (P = 0.017). Multivariate analysis found that age > 65 years, poor performance status, platelet count < 100,000/μL, serum albumin < 3.5 g/dL, serum creatinine ≥ 2.0 mg/dL, serum β2 microglobulin ≥ 3.5 mg/dL, the presence of extramedullary plasmacytoma, and the presence of chromosomal abnormalities were all found to be independent prognostic factors for OS. Conclusion In this study, we demonstrate improved survival of patients with multiple myeloma after the introduction of novel agents and autologous stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

Abstract 4902 Introduction Cytogenetics and fluorescent-in situ hybridization (FISH) are important outcome predictors in multiple myeloma (MM). There were only few small studies that investigated prognostic implication of FISH and/or conventional karyotyping in Korean MM patients. We investigated the incidences and prognostic significances of chromosomal abnormalities detected by FISH and/or conventional karyotyping among Korean MM patients. Patients and Methods We collected data of patients from Korean Myeloma Registry and performed retrospective analysis. We compared the survival of patients with chromosomal abnormalities and other clinical findings. Results From 2000 to 2009, total of 801 newly diagnosed myeloma patients were enrolled in this study. Median age of patients was 62 years. Median overall survival was 82 months, and median follow up of time was 92 months. Among the patients who had conventional karyotype analysis, 17.1% were complex karyotype, followed by del13q (7.4%), hyperdiploidy (7.6%), hypodiploidy (3.0%), and t(11;14) (3.9%). Among the patients who had FISH analysis, 22.8% were del 13q, followed by t(11;14) (18.2%), t(4;14) (13.7%), del17p (11.8%) and t(14;16) (5.9%). Univariate analyses revealed that complex karyotype (p Conclusions Our results showed that complex karyotype, hypodiploidy, t(4;14), and del13q by FISH and/or conventional karyotyping were negative prognostic factors for overall survival in univariate analyses. On multivariate analysis, low serum albumin level and percentage of plasma cells in bone marrow were independent risk factors for overall survival. In future, prospective trial with laboratory standardization is warranted for more reliable results from FISH and/or conventional karyotyping in MM patients. Disclosures Suh: Janssen Korea: Research Funding.

Abstract 2778 Poster Board II-754 Introduction: Interstitial deletions involving the long arm of chromosome 5, one of the good prognostic factors, are the most common chromosomal abnormality either as a sole or in combination with other abnormalities in myelodysplastic syndromes (MDS). However, the prognostic impact of del(5q) accompanied by additional chromosome abnormalities remains controversial. We investigated the hematologic, cytogenetic and prognostic features of del(5q) in MDS. Also, we mapped the deleted region on 5q by fluorescence in situ hybridization (FISH), whether the difference of deleted region between 5q- syndrome and MDS with del(5q) accompanied by additional abnormalities makes the clinical and prognostic differences. Methods: 137 adult patients, newly diagnosed as de novo MDS in Seoul National University Hospital from April 2000 through March 2009, were enrolled. We reclassified MDS subtypes according to WHO classification 2008. To compare the hematologic, cytogenetic and prognostic features according to presence of del(5q), we categorized the patients with del(5q) into 3 groups: patients with additional chromosomal abnormalities with del(5q) as 'MDS with del(5q)'; patients with other chromosomal abnormalities other than del(5q) as 'MDS with other chromosomal abnormalities (CA)'; and patients with isolated del(5q) as '5q- syndrome'. Also, the mapping with FISH for EGR1, CSF1R, and PDGFRβ on 5q, was performed in conjunction with G-banding to all patients and additional 16 patients with alleged del(5q) by G-banding from Korean MDS working party. Results: According to the new WHO classification of 2008, the 33 refractory anemia patients according to the previous WHO classification of 2001 were reclassified into refractory cytopenias with unilineage dysplasia (13 patients), refractory cytopenia with multilineage dysplasia (six patients) and MDS - unclassified (14 patients) (Fig 1). The median age of Korean MDS was 59 years, and the frequencies of 5q- syndrome and 5q deletion was 2.2% (3/137 patients) and 15.3%, respectively. Among 137 patients, 17 patients were grouped into 'MDS with del(5q)', and 53 patients into 'MDS with other CA'. The 'MDS with del(5q)' were significantly older and showed higher % of blasts in PB and BM than 'MDS with other CA'. And, they were categorized into higher risk group according to the International Prognostic Scoring System (IPSS) (Table 1). As a results of mapping for EGR1, PDGFRβ and CSF1R, deletion of all 3 regions was 93.3% in patients of 'MDS with del(5q)' and 66.7% in patients of '5q- syndrome', showing no difference in deleted genes between the two groups. Half (53%) of patients of 'MDS with del(5q)' accompanied complex abnormalities including chromosome 7 abnormalities. The del(5q) was detected only by FISH, showing discrepant results between G-banding and FISH analysis. Especially, marker chromosomes by G-banding in some patients were proved to be chromosome 5 with del(5q) by FISH. Conclusion: The biologic and prognostic features of MDS in Korea seem to be markedly different from those of Caucasian; younger age and low frequency of 5q- syndrome. The incidence of complex cytogenetic abnormalities including del(5q) was higher than that of Caucasian, while that of isolated del(5q) was quite low in Korea, which can explain that higher proportion of MDS with del(5q) belongs to higher risk IPSS group. And, we suggest FISH for del(5q) at initial diagnosis and during follow-up after treatment of MDS with alleged del(5q), since the presence of del(5q) in MDS is important for choosing the lenalidomide treatment. Disclosures: No relevant conflicts of interest to declare.

Abstract 2072 Poster Board II-49 Backgrounds Currently, there are many efforts to design risk-adapted strategies in newly diagnosed acute promyelocytic leukemia (APL) by modulating treatment intensity and those seem to be an efficient approach to minimize treatment-related morbidity and mortality (TRM) while maintain the potential in cure for each relapse-risk group. We had postulated that maintaining of Ara-C during induction therapy might have acceptable toxicities yet obtaining good CR in newly diagnosed APL, and idarubicin alone during consolidation periods might have excellent LFS and OS with low relapse rate. Patients and Methods Eighty six patients with newly diagnosed APL were enrolled in the “multicenter AML-2000 trial” after informed consents were obtained during the period of January 2000 to July 2007. For remission induction therapy, patients received oral ATRA (45mg/m2/d, maintained until CR) combined with idarubicin (12mg/m2/d, D1-D3) plus Ara-C (100mg/m2/d, D1-D7). After CR achievement, patients received 3 monthly consolidation courses consisting of idarubicin (12mg/m2/d, D1-D3) alone and maintenance therapy with ATRA (45mg/m2/d, D1-D15, every 2 month) alone had continued for 2 years. Total patients were divided into low-risk, intermediate-risk and high-risk groups according to a predictive model for relapse risk (Sanz score) based on pretreatment WBC and platelet count and the treatment outcomes were compared in the different risk groups. Results The median age of our cohort was 40 years old (range; 6-80) and median follow-up was 27 months (range; 1-90). The distribution of patients in the 3 risk groups was as follows ; 28 (32.6%) patients in low-risk, 40 (46.5%) in intermediate-risk and 18 (20.9%) in high-risk. Overall, CR was achieved in 78 (90.7%) of 86 patients. The CR rate according risk groups was 96.4% in low-risk, 87.5% in intermediate-risk, and 88.9% in high-risk group and there was no significant statistical difference among the different risk groups. During induction therapy, 48 (55.8%) patients experienced grade 3-4 treatment-related toxicity (TRT), mostly fever and infection (38.8% of all patients) and 6 (7.0%) patients died of treatment-related complications. During 3 consolidation courses, 25 (29.1%) of 78 patients experienced grade 3-4 TRT in 1st course, 27 (36.0%) of 75 patients in 2nd course, and 14 (28.0%) of 50 patients in 3rd course. Overall, 3 (3.5%) patients died of treatment-related complications in CR. The incidence of TRT and treatment-related mortality (TRM) during induction or consolidation therapy showed no significant statistical difference among the different risk groups. The relapse occurred in 6 (7.0%) patients; 2 cases in intermediate-risk and 4 cases in high-risk. However, none had relapsed in low risk group, 5 patients of relapsed patients relapsed during consolidation courses and only one patient, however, relapsed during maintenance therapy. The overall survival (OS) and leukemia-free survival (LFS) rate at 7 years in all of patients was 76.7% and 83.5%, respectively. The OS rate at 7 years was 92.9% in low-risk, 78.6% in intermediate-risk and 53.6% in high-risk group (P:0.04) and the LFS rate at 7 years was 96.4%, 83.4% and 62.2% respectively, showing the significant difference between 3 different risk groups (P:0.046). Conclusions This study indicates that our protocol composed of induction therapy with “3+7” chemotherapy plus ATRA followed by consolidations with three courses of idarubicin alone and maintenance therapy with ATRA alone yields a high CR rate and low relapse rate but minimal acceptable toxicities. Despite of adding Ara-C during induction therapy, we did not find much significant toxicities but having good CR rates, and despite of not adding any additional low/intermediate dose chemotherapies(ie, 6MP), we were able to observe significantly high relapse rate in low and intermediate risk group with excellent LFS and OS. Meanwhile, in high-risk group, the relapse rate was significantly higher than other risk groups and most of the relapses occurred in the middle of consolidation courses. This data suggests that our consolidation therapy composed of anthracycline alone may be not enough to minimize risk of relapse in high-risk group in contrast with the low and intermediate-risk groups. More intensive consolidation therapy combined with other effective, but get tolerable chemotherapies or hematopoietic stem cell transplantation in first CR or the combination of arsenic trioxide or others in front-line therapy should be considered in the patients with high-risk of relapse. Disclosures: No relevant conflicts of interest to declare.

Abstract 3810 Poster Board III-746 PURPOSE Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). The clinical data on specific benefits of deferasirox in transfusion-related iron overload patients with MDS or AA has been limited. METHODS: We have prospectively investigated the efficacy of deferasirox by serial measurement of s-ferritin level and LIC by R2-MRI in transfusional iron overload patients with MDS or AA. RESULTS: A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. Mean value of s-ferritin level in enrolled patients was 4,788 ng/ml in MDS and 4,188 ng/ml in AA at the time of deferasirox initiation. Mean value of LIC was 24.4 mg Fe/g dry weight in MDS and 22.4 mg Fe/g dry weight in AA. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients and was withheld If the s-ferritin falls below 500 ng/ml. Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 12 months of medication, s-ferritin level significantly decreased by 1824.0 ng/ml form baseline values, a reduction of 38.1% for patients with MDS (p Disclosures: No relevant conflicts of interest to declare.

In this report, we present a case of a patient with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia after renal transplantation. The patient, a 65-year-old man, had received a kidney transplantation 20 years prior to diagnosis with Ph+ precursor B-cell ALL. Because he was refractory to intensive chemotherapy and had refused to receive additional intensive chemotherapy, he was treated with imatinib and dexamethasone. While this patient experienced a complete hematologic and cytogenetic response, he did not show a complete molecular remission. Eighty days after imatinib combination therapy, the patient relapsed and died from intracerebral hemorrhage.

Cytogenetics is still being considered the most powerful single prognostic factor, which is useful to determine the types of post-remission therapy in AML, though various molecular markers are available for predicting the prognosis of AML patients. Most phase III studies have failed to demonstrate a clear advantage of allografting over chemotherapy in terms of overall survival because of significant risk of transplant-related mortality. Optimal post-remission therapies in terms of frequencies (number of treatment) or intensities are not decided yet. In this study, since 2000, we investigated that outcomes of post-remission therapies(high-dose cytarabine (HDAC) vs autologous stem cell transplantation (AutoSCT) vs allogeneic stem cell transplantation from sibling or unrelated donors (AlloSCT)) based on cytogenetic risk (GPG, Good prognosis group; IPG, Intermediate prognosis group; PPG, Poor prognosis group by MRC definition) on the AML patients who achieved complete remission after induction chemotherapy. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS in the different prognostic groups. Three plus seven (idarubicin 12mg/m2, D1–D3; cytarabine 100mg/m2, D1–D7) were given to de novo AML, secondary AML and therapy-related AML. Then, HDAC or AutoSCT was given after intermediate dose (8gm/m2) of cytarabine to the patients with GPG. Three times of post-remission therapy including HDAC, or AutoSCT followed by two times of post-remission therapy were given to IPG or PPG. If HLA-identical sibling was available, then AlloSCT underwent after 1st post-remission therapy. Since January, 2000, 506 patients(18 centers) were enrolled up to December, 2007. Among them, 92.3% was de novo AML, and GPG, IPG and PPG were, 23.1%, 62.1% and 14.8% respectively. Over all complete remission rate after 1st induction was 79.0% and CR rate in GPG, IPG, PPG were 92.0%, 81.0% and 43.9% respectively(P

Purpose: Patients with multiple myelma (MM) are at increased risk for developing thromboembolism (TE) compared with the general population. Introduction of thalidomide into the treatment of MM has resulted in the surprising increase of TE. We planned to identify incidence of TE and risk factors for the development of TE in Korean MM patients. Patients and Methods: Retrospective medical records review of Korean MM registry from 25 centers in Korea between 1997 and 2007 was performed. We assessed the incidence of arterial and venous TE in MM patients during thalidomide treatment. Potential risk factors for TE included disease status at thalidomide administration, concomitant use of other chemotherapeutic agents or steroid, past medical history and TE prophylaxis. Kaplan-Meier method for time variable from the first date of thalidomide to development of TE was used. Results: A total number of 360 MM patients (median age 61, range 32–88) received thalidomide. 23, 62 and 265 patients had stage ±, II, and III disease according to Durie-Salmon Staging respectively at the diagnosis, which was equivalent to 79, 146 and 112 patients for stage ±, II and III by International Staging System. 156 patients received thalidomide as frontline therapy, while 153 and 48 patients received thalidomide for progressive disease and relapsed disease respectively. 243, 139, 172 and 60 patients experienced treatment with steroid, alkylating agents, anthracyclin and bortezomib prior to thalidomide respectively. 9 patients had previous history of TE before thalidomide administration. 135 patients received aspirin as prophylaxis for TE while 3 and 2 patients received warfarin and low molecular weight heparin as prophylaxis. Median follow up duration was 29.2 months and median duration of thalidomide use was 8.13 months. During thalidomide treatment, 249 (69%) patients stopped thalidomide due to unsatisfactory effect or intolerable toxicity. 14 patients (3.9%) developed TE, where 12 with the venous TE and 2 with the arterial TE. There was no TE-related mortality. Site of the venous TE included lung (7 patients), lower extremity (4 patients), upper extremity (1 patient) and neck (1 patient). One patient had pulmonary and lower extremity TE at the same time. Arterial embolism developed in the cerebral and peripheral artery respectively. No single clinical parameter such as MM status, past medical history and treatment regimen was predictive marker for development of TE. Incidence of TE in patients who received thalidomide as a frontline therapy (7/156) was not different from that in patients who received thalidomide for progressive or relapsed disease (7/201, p=0.296). Prophylactic treatment for TE did not influence the development of TE (p=0.942). Conclusion: Incidence of TE during thalidomide treatment in Korean MM patients was low. No single clinical parameter was proven as a risk factor for TE. The prophylactic anticoagulation in Korean MM patients who will be treated with thalidomide is not necessary.