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// Da Jung Kim 1 , Ho Sup Lee 1 , Joon-Ho Moon 2 , Sang Kyun Sohn 2 , Hyeoung Joon Kim 3 , June-Won Cheong 4 , Deog-Yeon Jo 5 , Hawk Kim 6 , Hyewon Lee 7 , Soo-Mee Bang 8 , Won Sik Lee 9 , Yong Park 10 , Mark Hong Lee 11 , Jae Hoon Lee 12 , Sung Hwa Bae 13 , Min Kyoung Kim 14 and The Korean Society of Hematology AML/MDS Working Party 1 Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, Busan, South Korea 2 Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, South Korea 3 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, South Korea 4 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea 5 Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University, Daejeon, South Korea 6 Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea 7 Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, South Korea 8 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul, South Korea 9 Department of Internal Medicine, Busan Paik Hospital, Busan, South Korea 10 Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea 11 Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea 12 Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea 13 Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea 14 Department of Hematology-Oncology, Yeungnam University Medical Center, Yeungnam University School of Medicine, Daegu, South Korea Correspondence to: Ho Sup Lee, email: hs52silver@gmail.com Keywords: myelodysplastic syndrome, discontinuation, survival, decitabine, azacitidine Received: March 17, 2017 Accepted: April 28, 2017 Published: May 29, 2017 ABSTRACT It is often difficult to continue treatment with hypomethylating agent(HMA) in clinical practice because of problems such as toxicities, poor economics, etc. We compared clinical outcomes of those patients who continued HMA and those who discontinued HMA because of other causes, and evaluated factors associated with survival in those patients who discontinued HMA. Patients were divided into two groups: treatment failure, those who stopped treatment due to disease progression; and discontinuation, those who discontinued treatment because of other causes. The median progression free survival(PFS) was 9.2 months (range 7.7 – 10.7 months) vs 28.9 months (range 22.6 – 35.2) in the treatment failure and discontinuation groups, respectively ( P < 0.001). In a multivariate analysis, a lower risk by WPSS was an independent predictive factor for a longer PFS, and a lower risk by WPSS and median number of HMA cycles greater than seven were independent predictive factors for longer overall survival(OS) only in the discontinuation group. Patients who discontinued HMA without disease progression showed a prolonged survival than those who failed HMA treatment. Especially, a lower risk by WPSS and longer duration of HMA treatment may be predictive factors for a longer PFS and OS in patients who discontinued HMA.

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM. Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS). Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), β2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP. In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

This study investigated the effects of process conditions (anodization time, coloring treatment time, dye concentration) on the color of dye-treated anodized aluminum alloy 5052 (AA5052). The color change of the anodic layers and amount of dye adsorbed were quantitatively analyzed using a UV-vis spectrophotometer. The color of the anodic layer turned darker as the anodizing time, coloring treatment time, and dye concentration increased due to the amount of dye adsorbed by the layers. As the anodizing time increased, the thickness of the anodic layers also increased, and a growth in the number of nanopore sites resulted in a greater amount of dye being adsorbed, causing the darkening of the color. Increase in the coloring treatment time and dye concentration led to a greater amount of dye being adsorbed in the anodic layers, thereby contributing to the darkening of the color. Quantitative analysis in the depth direction of the anodic layer using glow discharge optical emission spectroscopy revealed that the dye was mostly adsorbed on the outer region of the anodic layer.

In this study, an electroless nickel (EN), electroless palladium (EP), and immersion gold (IG) (ENEPIG) multilayer coat was developed for application on BiTe-based thermoelectric materials to increase the bonding strength between BiTe-based materials and Cu electrodes in thermoelectric modules. The ENEPIG-plated thermoelectric module exhibited a bonding strength of over 11 MPa, which was approximately 40% higher than those of conventional EN-plated modules. According to the interfacial analysis of the bonding areas via a field emission electron probe micro analyzer (FE-EPMA), the Ni layers in ENEPIG and EN acted as diffusion barriers to inhibit the formation of brittle Sn-Te intermetallic compounds (IMCs). Sn-Cu-Pd and Sn-Cu IMCs were formed below the Ni-plated area at the bonding interface of the ENEPIG and EN-plated modules, respectively. However, Sn-Cu-Pd IMCs in the ENEPIG interface exhibited thicker and more homogeneous IMC layers after heat treatment compared to the Sn-Cu IMCs in the conventional EN interface. The wettability of the ENEPIG-plated BiTe surface was significantly greater than that of the EN-plated surface. This directly induced fewer and smaller pores on the bonding interface of the BiTe-based materials with ENEPIG plating compared to those with EN plating, thereby resulting in the higher bonding strength of ENEPIG-plated modules.

// Dok Hyun Yoon 1,* , Seok Jin Kim 2,* , Seong Hyun Jeong 3 , Dong-Yeop Shin 4 , Sung Hwa Bae 5 , Junshik Hong 6 , Seong Kyu Park 7 , Ho-Young Yhim 8 , Deok-Hwan Yang 9 , Hyewon Lee 10 , Hye Jin Kang 11 , Mark Hong Lee 12 , Hyeon-Seok Eom 10 , Jae-Yong Kwak 8 , Jae Hoon Lee 6 , Cheolwon Suh 1 and Won Seog Kim 2 1 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 2 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea 4 Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea 5 Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea 6 Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea 7 Department of Hematology/Oncology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea 8 Department of Internal Medicine, Chonbuk National University School of Medicine, Jeonju, Korea 9 Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea 10 Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea 11 Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea 12 Department of Hematology-Oncology, Konkuk University Medical Center, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Won Seog Kim, email: // Keywords : extranodal NK/T-cell lymphoma, nasal type; concurrent chemoradiotherapy; L-asparaginase; methotrexate; treatment Received : May15, 2016 Accepted : August 11, 2016 Published : August 16, 2016 Abstract We designed a new treatment protocol incorporating concurrent administration of L-asparaginase (to reduce the probability of systemic progression during concurrent chemoradiotherapy (CCRT)) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma, nasal type (ENKTL). CCRT comprised radiation (36–44 Gy) with weekly cisplatin (30 mg/m 2 ) and tri-weekly L-asparaginase (4 000 IU). Chemotherapy—MIDLE (methotrexate 3 g/m 2 on day 1, etoposide 100 mg/m 2 and Ifosfamide 1 000 mg/m 2 on days 2–3, dexamethasone 40 mg on days 1–4, and L-asparaginase 6 000 IU/m 2 on days 4, 6, 8, 10)—was repeated every 28 days for two cycles. One of the 28 patients developed distant lesions after CCRT. The final complete response rate was 82.1%. Four patients dropped out during or after their first MIDLE cycle due to toxicities (recurrent G3 hyperbilirubinemia [n = 1], G3-5 increased creatinine [n = 2], and G5 infection [n = 1]). With a median follow-up of 46 months (95% CI: 39–47 months), the estimated 3-year progression-free survival rate and overall survival rate were 74.1% and 81.5%, respectively. This MIDLE protocol may be effective for localized ENKTL. However, concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits.

Aim We performed a phase II study to evaluate the efficacy of combination chemotherapy consisting of gemcitabine, dexamethasone and oxaliplatin (GemDOx) as a biweekly regimen and salvage therapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Methods Gemcitabine (1000 mg/m2) and oxaliplatin (85 mg/m2) were administered intravenously on days 1 and 15, and dexamethasone (40 mg) was administered orally on days 1–4. Results Twenty-nine patients were enrolled, and most patients had diffuse large B-cell lymphoma (n = 18). The median age of the patients and median prior number of chemotherapy cycles were 53 (range, 26–74) years and 1 (range, 1–4) cycle, respectively. Only 17 (58.6%) and 9 (31.0%) patients completed two or more and four or more cycles, respectively, and the median number of received cycles was two (range, 1–8). Overall response rates were 27.6% (complete response in 13.8%) among intent-to-treat patients and 47.1% (complete response in 23.5%) among patients who had received at least two GemDOx cycles. Median progression-free survival and median overall survival were 3.9 and 20.5 months, respectively. The most-frequent grade 3 or 4 toxicity was neutropenia (22.9%), and no grade 3 or 4 peripheral neurotoxicity was noted. Conclusion GemDOx chemotherapy, therefore, showed modest activity against relapsed or refractory aggressive NHL, although toxicities were acceptable.

We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine-antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p = 1.000), acute GvHD (p = 0.769), grade 3/4 acute GvHD (p = 0.258), chronic GvHD (p = 0.173), extensive chronic GvHD (p = 0.099), primary neutrophil engraftment failure (p = 1.000), secondary graft failure (p = 1.000) and platelet engraftment failure (p = 0.505) were similar. Time to neutrophil engraftment was faster in haploFD (p = 0.003), while the cumulative incidence of platelet engraftment was similar (p = 0.505). Overall survival was also similar between AD and haploFD (p = 0.730). In conclusion, alloHCT from haploFD in sAA was comparable with alloHCT from AD, but extensive chronic GvHD seemed frequent in haploFD. Therefore alloHCT from haploFD could be an alternative approach for alloHCT from AD in adult sAA.

In this study, a method for electroless Ni-P plating with excellent adhesion via chemical wet etching to fabricate Bi-Te thermoelectric modules is proposed. The electroless Ni-P plating formed through the proposed method showed excellent adherence without peeling, even under heat treatment of 200 °C for 24 h. Wet etching and electroless Ni-P plating was performed on a Bi-Te thermoelectric module, which showed the excellent bond strength of approximately 10 MPa. The surface roughness of the Bi-Te thermoelectric element was increased significantly by the wet etching process, which secured the adherence of the Ni-P plating by anchoring to this induced surface roughness.

A method for directly bonding thermoelectric elements onto copper electrodes without applying a solder paste was developed in this study. A tin coating of thickness approximately 50

In this study, electrolytic etching, anodic oxidation, and copper electroplating were applied to aluminum to produce a plate on which a copper circuit for a thermoelectric module was formed. An oxide film insulating layer was formed on the aluminum through anodic oxidation, and platinum was coated by sputtering to produce conductivity. Finally, copper electroplating was performed directly on the substrate. In this structure, the copper plating layer on the insulating layer served as a conductive layer in the circuit. The adhesion of the copper plating layer was improved by electrolytic etching. As a result, the thermoelectric module fabricated in this study showed excellent adhesion and good insulation characteristics. It is expected that our findings can contribute to the manufacture of plates applicable to thermoelectric modules with high dissipation performance.

581 Copyrightc 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 2014. 11. 28 Revised: 2015. 3. 4 Accepted: 2015. 4. 29

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P

Relapsed or refractory acute myeloid leukemia (R/R AML) in elderly (≥60 yr old) patients were eligible. Induction chemotherapy consisted fludarabine and cytarabine (ARAC) as a 24-hr CI without idarubicin (C-FLAG), which was compared with the results of C-FLAG with idarubicin (CI-FLAG2) in younger patients' trial. A total of 33 and 68 patients were enrolled in C-FLAG and CI-FLAG2, respectively. CR, CRp, and CRi were achieved in 10 (30.3%), 3 (9.1%), and 2 (6.1%), respectively. When comparing outcomes between C-FLAG and CI-FLAG2, there were no difference in terms of CR rate (P = 0.572) and objective response rate (ORR; P = 0.899). Favorable predictors on ORR in C-FLAG were PB WBC ≤ 20K/uL at salvage (P = 0.024) and early evaluation peripheral BLAST = 0% (P = 0.013) on multivariate analysis. The overall survival of patients who achieve CR/CRp/CRi showed significantly prolonged survival compared with patients who did not in C-FLAG (P

BACKGROUND Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality. STUDY DESIGN AND METHODS This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled. RESULTS Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was −65 ng/mL in AA (p = 0.037), −647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and −552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was −0.17 μmol/L in AA, −0.21 μmol/L in MDS-LR, and −0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%). CONCLUSION DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups.

The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.

We previously assessed continuous infusion (CI) of fludarabine and cytarabine plus idarubicin (CI-FLAG1) for patients under 65 years of age with resistant acute myeloid leukemia. Induction chemotherapy consisted of idarubicin (IDA) plus fludarabine and cytarabine (ARAC) as a 24-hour CI. In response to induction, 31.6% of patients achieved complete remission (CR) and in 68.4% the treatment failed. We concluded that CI-FLAG1 carried a high risk of toxicity and reduced CI-FLAG doses were recommended. Therefore, we revised the protocol (CI-FLAG2) by reducing the dose of IDA and ARAC. In total, 38 and 68 patients were enrolled into CI-FLAG1 and CI-FLAG2, respectively. When comparing outcomes between CI-FLAG1 and CI-FLAG2, there were no differences in terms of the CR rate (p = 0.306) and the overall response rate (ORR; p = 0.206). The treatment failure patterns were different between CI-FLAG1 and CI-FLAG2. The median overall survival showed only a trend towards longer survival in CI-FLAG2 (p = 0.074). Among intermediate-risk patients, there were high response rates favoring CI-FLAG2 in terms of the CR rate (p = 0.108), the ORR (p = 0.031), and overall survival (p = 0.033). This represented a relatively improved response rate compared to our previous study. There was decreased aplasia with dose reductions at the expense of increased resistance. A reduced dose of CI-FLAG might be most beneficial for intermediate-risk groups.

This multicenter phase II clinical trial was designed to evaluate the efficacy and safety of weekly Genexol-PM® and gemcitabine combination chemotherapy in patients with unresectable or metastatic biliary tract cancer. Patients and methods Patients received 100 mg/m2 Genexol-PM® and 1,000 mg/m2 gemcitabine intravenously on days 1 and 8 every 21 days. Results Out of 39 patients, there were 10 partial responses (25.6%) and 18 with stable diseases (46.2%) were confirmed with median response duration 4.1 months. The median progression-free survival was 5.9±1.6 months and overall survival 11.9±1.4 months. The median number of cycles administered was 4.0 (range=1-10). Grade 3 or more neutropenia occurred in 12 patients (26.7%). The most common grade 3/4 non-hematological toxicities were febrile neutropenia (13.4%) and elevation of liver enzymes (6.7%). Conclusion Weekly Genexol-PM® combined with gemcitabine demonstrated sufficient antitumor activity to warrant further development when used as first-line chemotherapy for advanced biliary tract cancer.

B ackground The advent of new agents has contributed to the prolonged survival of multiple myeloma (MM) patients. From the Durie-Salmon staging system, international staging system (ISS) and recently, revised ISS (R-ISS) have been developed to better prognosticate the survival of MM. R-ISS includes chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH) and lactate dehydrogenase (LDH) in addition to the ISS. However, the R-ISS has still some limitations in the real clinical settings, as it has enrolled patients exclusively on clinical trials which includes more young patients (age < 65 years old), contains non-standardized iFISH results and has short median follow-up duration. The first-line drugs used in the patients could also affect the prognosis. Therefore, a more detailed and standardized but also convenient prognostic system is needed with clinical findings commonly observed in MM patients treated with new agents in the real clinical world. Patient and Method Adult patients who were confirmed multiple myeloma between January, 2011 to December, 2017 and patients who had received thalidomide and/or bortezomib or lenalidomide-based chemotherapy as a first-line treatment were included for the analysis. A total of 861 patients from 13 centers participating Korean multiple myeloma working party were analyzed. Baseline serum albumin, serum ß2-microglobulin, cytogenetics by iFISH, LDH (lactate dehydrogenase), ALC (absolute lymphocyte count), CRP (C-reactive protein) and ferritin were measured within 4 weeks before beginning the first line of chemotherapy. Each factors of age ≥ 65 years, serum ß2-microglobulin ≥ 5.5 mg/L, LDH > normal, cytogenetic high risk by FISH (del17p, t(4;14), t(14;16)), ALC < 1500/mm3, CRP ≥ 1.5 mg/dL, and ferritin ≥ 500 ng/mL were defined as abnormal findings, which were given 1 point (Table 1) and the sum of points were used to discriminate inflammatory factor-based staging system (IFBSS). IFBSS were defined as follows: Stage I (point 0), stage II (point 2-3), stage III (point 4-5), and stage IV (point 5-7). Overall survival (OS) was defined by the date of MM diagnosis to the date of death by any cause or follow-up loss. Results Baseline characteristics of the patients were as listed in Table 2. With a median follow-up duration of 22.70 months (range, 0.20-86.80 months), age ≥ 65 years, serum ß2-microglobulin ≥ 5.5 mg/L, LDH > normal, cytogenetic high risk by FISH (del17p, t(4;14), t(14;16)), ALC < 1500/mm3, CRP ≥ 1.5 mg/dL, and ferritin ≥ 500 ng/mL showed significant higher OS by univariate and multivariate analysis. Albumin < 3.5 mg/dL were excluded into the staging system due the unpredictability to OS in univariate analysis (Table 3). Study groups of inflammatory factor-based scoring system comprised of 61 patients in stage I, 395 patients in stage II, 189 patients in stage III and 36 patients in stage IV. The median OS were not reached in stage I and II, stage III and IV showed a median OS of 36.57 months (95%CI, 33.96-.39.18) and 17.60 months (95%CI, 9.16-.26.04). The OS according to the IFBSS showed significant differences (P < 0.001), which predicted OS better compared with conventional ISS and R-ISS (Table 4). Conclusion In the new agent era, inflammatory factors incorporated into the staging system can better discriminate prognosis of multiple myeloma patients compared to the ISS or R-ISS. Validation of this finding in a larger cohort is needed to expand usage of this new staging system. Disclosures Yoon: Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kyowa Hako Kirin: Research Funding; Janssen: Consultancy; Yuhan Pharma: Research Funding; Genentech, Inc.: Research Funding; MSD: Consultancy.

In this study, electroless-plating of a nickel-phosphor (Ni&ndash, P) thin film on surface-controlled thermoelectric elements was developed to significantly increase the bonding strength between Bi&ndash, Te materials and copper (Cu) electrodes in thermoelectric modules. Without electroless Ni&ndash, P plating, the effect of surface roughness on the bonding strength was negligible. Brittle SnTe intermetallic compounds were formed at the bonding interface of the thermoelectric elements and defects such as pores were generated at the bonding interface owing to poor wettability with the solder. However, defects were not present at the bonding interface of the specimen subjected to electroless Ni&ndash, P plating, and the electroless Ni&ndash, P plating layer acted as a diffusion barrier toward Sn and Te. The bonding strength was higher when the specimen was subjected to Ni&ndash, P plating compared with that without Ni&ndash, P plating, and it improved with increasing surface roughness. As electroless Ni&ndash, P plating improved the wettability with molten solder, the increase in bonding strength was attributed to the formation of a thicker solder reaction layer below the bonding interface owing to an increase in the bonding interface with the solder at higher surface roughness.

Purpose We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Materials and Methods A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively. Results The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p

The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥10 × 109/L, platelet

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

We performed a phase II study to evaluate the efficacy of combination chemotherapy consisting of gemcitabine, dexamethasone and oxaliplatin (GemDOx) as a biweekly regimen and salvage therapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).Gemcitabine (1000 mg/m(2) ) and oxaliplatin (85 mg/m(2) ) were administered intravenously on days 1 and 15, and dexamethasone (40 mg) was administered orally on days 1-4.Twenty-nine patients were enrolled, and most patients had diffuse large B-cell lymphoma (n = 18). The median age of the patients and median prior number of chemotherapy cycles were 53 (range, 26-74) years and 1 (range, 1-4) cycle, respectively. Only 17 (58.6%) and 9 (31.0%) patients completed two or more and four or more cycles, respectively, and the median number of received cycles was two (range, 1-8). Overall response rates were 27.6% (complete response in 13.8%) among intent-to-treat patients and 47.1% (complete response in 23.5%) among patients who had received at least two GemDOx cycles. Median progression-free survival and median overall survival were 3.9 and 20.5 months, respectively. The most-frequent grade 3 or 4 toxicity was neutropenia (22.9%), and no grade 3 or 4 peripheral neurotoxicity was noted.GemDOx chemotherapy, therefore, showed modest activity against relapsed or refractory aggressive NHL, although toxicities were acceptable.

Background To investigate the efficacy, safety, and tolerability of weekly docetaxel treatment in advanced non-small cell lung cancer (NSCLC) patients in Korea. Methods This prospective observational study included Korean advanced NSCLC patients with Eastern Cooperative Oncology Group performance status

There has been controversy surrounding Waldeyer’s ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5–4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P

Objective: To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain. Settings and Design: Multicenter, prospective, open-label, phase IV study. Participants: Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP. Interventions: Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlledrelease oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14. Main Outcomes: BTP medication frequency on days 7 and 14, compared to baseline. Results: Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p < 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p < 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness. Conclusion: Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.

One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis.The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay.Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p0.05).The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer.

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2 per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2 per day times 3 days) in addition to cytarabine (200 mg/m2 per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

Introduction Diffuse large B cell lymphoma (DLBCL) of primary nodal (PN) or primary extranodal (PEN) origin may differ immunophenotypically, in that PEN lymphoma cells may originate from activated rather than germinal center B (GCB) cells. We evaluated the relationship between DLBCL clinicopathological features, including expression of B-cell differentiation markers, and primary tumor site. Patients and Methods Expression of CD10, Bcl-6, Bcl-2, and MUM1 was determined in paraffin-embedded tissues from 123 patients with DLBCL. Results Of the 123 patients with DLBCL, 40 (32.5%) had the GCB and 83 (67.5%) had the non-GCB phenotype. Fifty-one patients (42%) showed disease involvement at PEN sites, including 29 with disease in the gastrointestinal (GI) tract (14 in the stomach, 15 in the intestine). Of these 51 patients, 16 (31.4%) were classified with the GCB and 35 (68.5%) with the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes among primary sites. Of the 72 patients with PN DLBCL, 22 (31%) had the GCB and 50 (69%) had the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes between patients with PN and PEN DLBCL. Although lactate dehydrogenase (LDH) concentration > normal, stage >II, and rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) treatment were independent predictors of overall survival (OS), GCB subtype, and presence of PEN disease failed to predict survival upon multivariate analysis. Conclusion There was no difference in GCB and non-GCB phenotypes between patients with PN and PEN DLBCLs. Additional studies are needed to further assess molecular differences between the two groups.

Upfront allogeneic hematopoietic cell transplantation (alloHCT) as first line therapy for older than 40 or 50 years is not usually recommended for severe aplastic anemia patients even though there are suitable matched sibling donors because they usually have poor outcomes after alloHCT. Therefore, first line immune suppression therapy (IST) is recommended. However, current outstanding alloHCT outcome can make it possible to try upfront alloHCT even in older AA patients. The purpose of this retrospective study is to determine the transplantation-related results in AA patients older than 40 years. This study collected data retrospectively for older AA patients. Congenital bone marrow failure was excluded from this study. alloHCT was divided as upfront and second alloHCT according to prior IST. Total 129 patients were enrolled in this study from 2001 to 2017. Age at diagnosis and at alloHCT were 25 to 63 (median 48.0) years and 40.3-64.9 (median 49.1) years, respectively. Median time from diagnosis to alloHCT was 5.2 (range, 1-234.1) months. Upfront and second alloHCT were 42 and 87 patients, respectively. Upfront alloHCT received more stem cells from related donors, more BM stem cells and more fludarabine conditioning compared with second alloHCT (83.3% vs. 58.6%, p=0.005; 52.4% vs. 74.7%, p=0.011; 52.4% vs. 30.2%, p=0.015, respectively). However, ABO mismatching (p=0.747), TBI conditioning (p=0.547), cyclophosphamide conditioning (p=0.114), ATG conditioning (p=0.483) were similar between upfront and second alloHCT. Any engraftment failure, neutrophil engraftment failure and platelet engraftment failure were similar between upfront and second alloHCT (28.6% vs. 28.7%, p=0.985; 19.0% vs. 18.4%, p=0.928; 19.0% vs. 34.5%, p=0.072). Hepatic SOS, acute GvHD and chronic GvHD were also similar between upfront and second alloHCT (4.8% vs. 5.7%, p=0.817; 28.6% vs. 36.5%, p=0.376; 19.0% vs. 19.5%, p=0.947). Survival rates at 1Y, 2Y, 3Y and 5Y were 90.7, 82.2, 73.5 and 64.3%, respectively. Survival rates at 5 years in upfront and second alloHCT were 76.2 and 54.1%, respectively (p=0.059). Survival rates at 5 years (5YSR) in age 40-50y, 50-60y, and older than 60y were 64.1, 62.4 and 50.0%, respectively (p=0.349). alloHCT from matched related donor or other donors had similar survival rates (p=0.404). However, upfront alloHCT showed superior survival rate (5YSR 76.5% vs. 53.2%, p=0.114) without statistical significance compared with second alloHCT even in matched related donor subgroup. This trend is similar in alternative donor subgroup (5YSR 75.0% in upfront alloHCT vs. 54.9% in second alloHCT, p=0.459). alloHCT in older AA showed promising results even in patient older than 60 years although upfront alloHCT showed marginal statistical superiority. In conclusion, upfront alloHCT in older AA needs further confirmation by prospective studies. Disclosures No relevant conflicts of interest to declare.

Introduction Four cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapy for patients aged less than 65 years with newly diagnosed multiple myeloma (NDMM). Complete remission (CR) status before ASCT is an important prognostic factor for progression-free survival (PFS). We analyzed whether two additional cycles of VTD improved the pre- and post-transplant responses as well as PFS compared to the four cycles of VTD induction therapy. Methods A total of 222 patients with NDMM between September 2014 and August 2016 from eleven hospitals in South Korea were included in the current study. The patients received at least four or more cycles of VTD induction therapy before administration of high-dose therapy (HDT, melphalan 200mg/m2) followed by ASCT. VTD regimen was consisted of bortezomib subcutaneous infusion (1.3 mg/m2 on days 1, 4, 8, and 11), thalidomide (100 mg daily), and dexamethasone (40 mg on days 1-4, 8-11), which was administered every 4 weeks. Results The median age was 57 years (range 30−64 years), and 120 patients (61.9%) were male. Revised international scoring system (R-ISS) classified 59 (30.4%), 86 (44.3%), and 49 patients (25.3%) as stage I, II, and III, respectively. VTD induction was administered 4 cycles in 194 patients (VTD4, 67.5%) and more than 4 cycles in 63 (VTD6, 32.5%) before HDT. Patient characteristics at diagnosis did not differ between VTD4 and VTD6. CR rate before HDT was significantly higher in VTD6 than VTD4 (31.7% vs 13.0%, P = 0.003). However, CR rate after HDT/ASCT was similar between VTD4 and VTD6 (69.0% vs 65.5%, P = 0.726). There was no difference in the incidence of peripheral neuropathy (PN) (≥ grade 2 or that required dose reduction) between two groups. The median follow-up duration was 18.0 months (range 7.0-43.8 months). The 2-year PFS did not differ between the two groups (51.7 ±5.7% in VTD4 and 62.1±8.6% in VTD6, P = 0.240). Multivariate analysis revealed that the achievement of CR was a favorable prognostic factor for PFS (HR 0.27 [0.08−0.90], P = 0.034). Deletion 17p (HR 2.87 [1.01−7.92], P = 0.048) and t(4;14) (HR 3.38 [1.76−6.48], P < 0.001) in FISH were adverse prognostic factors for PFS. Patients with stage I/II by R-ISS receiving additional two cycles of VTD showed prolonged PFS (median PFS not reached vs. 27.6 months, P = 0.034). In the multivariate analysis, VTD6 was a favorable prognostic factor for PFS for patients with stage I/II by R-ISS, (HR 0.11 [0.02−0.52], P = 0.005). Conclusion CR rates increased with additional cycles of VTD induction therapy for NDMM. However, the PFS benefit was observed only in patients with R-ISS stage I/II. For patients with high-risk MM, intensive induction therapy that overcome poor prognostic factors should be administered to improve long-term outcomes. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

In this study, a method for electroless Ni–P plating with excellent adhesion via chemical wet etching to fabricate a Bi2Te3 thermoelectric module is proposed. The electroless Ni–P plating formed through the proposed process showed excellent adherence and did not desquamate, even under heat treatment at 200 °C for 24 h. Wet etching and electroless Ni–P plating was performed on a Bi2Te3 thermoelectric module, which showed excellent bond strength at approximately 10 MPa. The surface roughness of the Bi2Te3 thermoelectric element increased largely due to wet etching, and the adherence of the Ni–P plating could be secured by means of the anchor (surface roughness) effect.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of S-1, paclitaxel plus cisplatin in patients with advanced gastric cancer.Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 80 mg/m² plus cisplatin 30 mg/m² on days 1, 8 and S-1 35 mg/m² orally twice daily on days 1-14 based on a 3-week cycle.Forty-four patients were enrolled in the current study, among whom 38 were assessable for efficacy and all assessable for toxicity. Two complete response and 24 partial responses were confirmed, giving an overall response rate of 59.1%. At a median follow-up of 11.4 months, the median time to progression and median overall survival was 9.4 (95% CI 6.8-12.1) months and 11.2 (95% CI 7.6-14.8) months, respectively. Grade 3/4 neutropenia occurred in 45 events (20.9%) and febrile neutropenia was observed in five events (2.3%). The common non-hematologic toxicity was nausea (grade 1/2, 27.2%) and diarrhea (grade 1/2, 9.0%).The combination of S-1, paclitaxel and cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay.During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) -535GT polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423-6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P0.001 and 0.001, respectively).The MGMT -535GT polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.

Objective This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. Patients and methods: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500mg/m 2 every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. Results The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4–12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8–57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17–5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19–10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0–1 [hazards ratio (HR)=0.331, 95% CI 0.135–0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283–0.899) were independent factors for prolongation of overall survival.Conclusions Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.

The objective of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination chemotherapy in patients with metastatic esophageal cancer.Patients with untreated metastatic squamous cell esophageal cancer, which was histologically proven with at least one measurable lesion, were eligible for the study. Docetaxel 70 mg/m(2) and cisplatin 70 mg/m(2) were intravenously given on day 1 of 21 days schedule.From December 2004 to December 2007, total of 39 patients (M/F = 39/0) were enrolled. The median age was 65 years. Thirty-four patients were evaluable for response. There were 3 (7.7%) complete remission, 10 (25.6%) partial remission, 11 (28.2%) stable disease, and 10 (25.6%) progression disease. The objective tumor response rate was 33.3% in intention-to-treat (ITT). Median PFS was 5.0 months and median survival was 8.3 months. Median number of cycles administered was 3. The relative dose intensity of docetaxel and cisplatin was 92 and 91%, respectively. This treatment was comparatively tolerated with grade 3/4 neutropenia in 20.5%/10.3%, grade 3 infection in 2.6% of patients.Docetaxel plus cisplatin combination chemotherapy showed promising antitumor activity with manageable toxicities in patients with metastatic squamous esophageal cancer.

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 present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

Primary retroperitoneal mucinous cystadenocarcinoma is a rare tumor. Only about 30 such cases have been reported in the worldwide literature, and a few Korean cases have been reported. The pathogenesis is not clear, and coelomic metaplasia of the retroperitoneal mesothelium has gained wide support. There is no consensus on the appropriate treatment, but surgical exploration is needed for the diagnosis and treatment, and adjuvant chemotherapy may be recommended following complete surgical excision. The long-term prognosis has not been established. We report here on a 32-year-old woman who was diagnosed as having a retroperitoneal mucinous cystadenocarcinoma with mural nodules of sarcomatoid change. Tumor excision and adjuvant chemotherapy were done and the patient is doing well without any evidence of recurrence at 42 months postoperatively.

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph(+) ) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P0.0001), and overall survival (P = 0.002). During the initial phase of treatment of patients with Ph(+) ALL, it is important to maintain imatinib dose intensity.

The current phase II clinical study was conducted to evaluate the efficacy and safety of weekly docetaxel alone, and weekly docetaxel-plus-oxaliplatin, as a second-line chemotherapy in patients with cisplatin-refractory advanced gastric cancer.We enrolled patients with histologically confirmed gastric adenocarcinoma whose disease had progressed after cisplatin-based regimens. Patients were randomly assigned to receive docetaxel alone (36 mg/m(2), days 1 and 8) or docetaxel (36 mg/m(2), days 1 and 8) and oxaliplatin (80 mg/m(2), day 1) combination therapy every three weeks.This trial was terminated early due to poor patient accrual rate. From January 2009 to January 2012, a total of 52 patients were enrolled in the current study from six centers: 27 patients in the docetaxel monotherapy arm and 25 patients in the docetaxel/oxaliplatin combination arm. Fifty-two patients were assessable for efficacy, and response rates as follows (response rate: 14.8% in the monotherapy arm, 24.0% in the combination arm; disease control rate: 48.1% in the monotherapy arm, 76.0% in the combination arm. The median progression-free survival was 2.0 (95% confidence interval=1.2-2.9) months in the monotherapy arm and 4.9 (95% confidence interval=3.6-6.6) months in the combination arm (p=0.002). The most common grade 3 or 4 adverse event was neutropenia (14% for monotherapy versus 32% for combination). No treatment-related mortality was observed.Weekly docetaxel and weekly docetaxel-plus-oxalipaltin regimens were found to be well-tolerated and effective as a second-line chemotherapy for patients with advanced gastric cancer.

The objective of this study was to review the natural history of extrapulmonary small cell carcinoma (EPSCC) with specific emphasis on clinical features, response to treatment and survival. The records of all patients (n=34) with EPSCC treated at Yeungnam University Medical Center and Catholic University of Daegu Medical Center between 1998 and 2005 were retrieved and reviewed. The primary sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas and stomach in 5 patients each (14.7%); other sites included were the cervix, abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had limited disease. The median survival of all patients was 14 months. Independent prognostic factors included stage and primary tumor location. The prognosis for the patients with extensive disease and in the gastrointestinal group was unfavorable. EPSCC is a non homogeneous disease entity. As a result of its frequent recurrence, multimodal therapy has a better outcome even in cases of limited disease. Combination chemotherapy plays a central role for treatment of extensive disease in EPSCC. Further multicenter studies are now needed to determine more details regarding disease sub-class and optimal treatment modality.

TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic micro-angiopathy. Although most cases are held to be idiopathic, its association with malignancy iswellrecognizedanditusuallyoccursattheterminalstageofcancer.Bonemarrownecrosis(BMN)is another rare disorder defined pathologically as the necrosis of myeloid tissue and medullarystromawithpreservationofbone.Whilehematologicmalignancyisthemostcommonunderlyingdisease associated with BMN, it can also be caused by solid tumors. Neither TTP nor BMNassociated with colon cancer has been reported. We describe here a patient with the rare asso-ciation of TTP and BMN displayed as the first manifestation of an advanced colon cancer. Theanemia and thrombocytopenia responded not to plasma exchange but to the combinationchemotherapy. This case indicates that metastatic cancer should be included in the differentialdiagnosis of TTP and BMN, and that the chemotherapy may improve the detrimental clinicalcourse.Key words: thrombotic thrombocytopenic purpura – bone marrow necrosis – colon cancer –microangiopathic hemolytic anemia

PURPOSE This study was conducted to evaluate the efficacy and safety of combination chemotherapy, with docetaxel and cisplatin, as a first line treatment for advanced non-small cell lung cancer. MATERIALS AND METHODS Between March 1998 and December 2001, 35 patients with advanced non-small cell lung cancer were enrolled in this study. The patients were treated at 3-week intervals, with one course of a regimen consisting of docetaxel (75 mg/m2 IV for 1 hours) on day 1 and cisplatin (60 mg/m2 IV) on day 2. RESULTS The median age of the patients was 60.3 years. Of the 35 patients, 20 and 15 had stage IIIb and stage IV diseases, respectively. A complete response was observed in 1 patient and partial response in 15, with an overall response rate of 46%. The overall median survival duration was 40.3+/-25.2 weeks. The median time to progression and response duration were 21.6+/-5.5 and 15.1+/-5.9 weeks, respectively. The survival duration was statistically significantly longer in the response group (50.6 weeks) than in the non-response group (31.6 weeks) (p

Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality.This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled.Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was -0.17 μmol/L in AA, -0.21 μmol/L in MDS-LR, and -0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%).DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups.

Background. Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL). Methods. Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m2 on days 1–3; methotrextate 30 mg/m2 on days 3 and 10; etoposide 100 mg/m2 on days 1–3; and prednisolone 60 mg/m2 per day on days 1–5) followed by involved field radiotherapy (IFRT). Results. Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively. Conclusion. Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.