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Background JAK2 mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2 allele burden is under investigation. Methods We retrospectively evaluated the impact of the JAK2 V617F allele burden on clinical characteristics and outcomes of JAK2 V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2 V617F allele burden was measured using sequencing. Results Altogether, 127 patients with JAK2 V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8- year OS based on the JAK2 V617F allele burden was not significant. Conclusion The JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.

Breast cancer is the most common female cancer in the world. Despite the active research on metastatic breast cancer, the treatment of breast cancer patients is still difficult because the mechanism is not well known. Therefore, research on new targets and mechanisms for diagnosis and treatment of breast cancer patients is required. On the other hand, microRNA (miRNA) has the advantage of simultaneously regulating the expression of many target genes, so it has been proposed as an effective biomarker for the treatment of various diseases including cancer. This study analyzed the role and mechanism of DBC2 (deleted in breast cancer 2), which is known to inhibit its expression in breast cancer, and proposed microRNA (miR)-5088-5p, which regulates its expression. It was revealed that the biogenesis of miR-5088-5p was upregulated by hypomethylation of its promoter, promoted by Fyn, and was involved in malignancy in breast cancer. With the use of the cellular level, clinical samples, and published data, we verified that the expression patterns of DBC2 and miR-5088-5p were negatively related, suggesting the potential as novel biomarkers for the diagnosis of breast cancer patients., Graphical abstract, The effects of DBC2, which is downregulated in breast cancer, and miR-5088-5p, which regulates its expression, on malignancy of breast cancer were studied. It was confirmed that miR-5088-5p expression was increased by Fyn induced its hypomethylation. Therefore, DBC2 and miR-5088-5p have potential as new biomarkers for diagnosing breast cancer malignancy.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Several high-dose therapy (HDT) conditioning regimens have been used to treat non-Hodgkin's lymphoma (NHL), such as bis-chloroethylnitrosourea (BCNU)/etoposide/cytosine arabinoside/melphalan (BEAM), BCNU/etoposide/cytosine arabinoside/cyclophosphamide (BEAC), and cyclophosphamide/BCNU/etoposide (CBV). BCNU is an active drug in HDT of NHL, but the supply is limited in some countries, including Korea. Busulfan has been used in allogeneic and autologous stem cell transplantation (ASCT). This phase II study evaluated the efficacy of busulfan/melphalan/etoposide (BuME) as a conditioning regimen for HDT in relapsed or high-risk NHL. The regimen consisted of intravenous busulfan (3.2 mg/kg/day) on days -8, -7, and -6, etoposide (400 mg/m2 /day) on days -5 and -4, and melphalan (50 mg/m2 /day) on days -3 and -2. A total of 46 patients were included in the study, with 36 (78.3%) achieving a complete response after ASCT. The 2-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 46.7% (95% CI, 31.8-60.4%) and 63.7% (95% CI, 47.7-76.0%), respectively. There was no development of veno-occlusive disease and no treatment-related deaths within 100 days after ASCT. These results indicate that a BuME regimen is well-tolerated and effective for patients with relapsed or high-risk NHL, and may be comparable to some previously used regimens. This regimen may be useful as a substitute for BCNU-containing regimens.

Background A high number of focal lesions (FL) detected using PET/CT at diagnosis were found to be associated with adverse prognosis along with Revised International Staging System (R-ISS). In present study, we combined R-ISS with FL using PET/CT to design a reliable and easily applicable risk stratification system in patients with newly diagnosed MM (NDMM). Methods In training cohort, the data of 380 patients with NDMM who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis from 10 hospitals of the Korean Multiple Myeloma Working Party were retrospectively analyzed. All patients were classified by R-ISS and were treated by frontline therapy with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD). The K-adaptive partitioning algorithm was adopted to develop the new risk groups with homogeneous survival. Sixty-seven patients in external validation cohort were additionally collected to confirm reproducibility of the new risk groups. Results In the training cohort, 199 patients (52.4%) showed FL > 3 using PET/CT at diagnosis. R-ISS stages I, II, and III were 78 patients (20.5%), 230 (60.5%), and 72 (18.9%), respectively. The combined R-ISS with PET/CT newly allocated NDMM patients into four groups: R-ISS/PET stage I (n=30; R-ISS I with FL≤3), stage II (n=149; R-ISS I with FL>3 and R-ISS II with FL≤3), stage III (n=166; R-ISS II with FL>3 and R-ISS III with FL≤3), and stage IV (n=35; R-ISS III with FL>3). The new R-ISS/PET showed significantly pronounced survival differences according to stages. Two-year overall survival (OS) rates were 96.6%, 89.5%, 75.0%, and 57.9% (p < 0.001), and 2-year progression-free survival (PFS) rates were 86.9%, 65.1%, 41.9%, and 15.2% (p < 0.001) in stages I, II, III, and IV, respectively. The prognostic role of the R-ISS/PET for survival outcomes was also confirmed in different subgroups classified by transplant eligibility and by types of treatments. In the external validation cohort, the new R-ISS/PET was successfully implemented. Two-year OS rates for were 100%, 89.9%, 82.6%, and 42.0% for R-ISS/PET I, II, III, and IV, respectively (p = 0.001). PFS rates at 2 years for each R-ISS/PET were 100%, 74.5%, 57.9%, and 25.6%, respectively (p = 0.004). In the multivariate Cox analysis for survival outcome, R-ISS/PET was a significant factor and could predict long-term outcomes with regard to OS: stage II vs. I (HR 2.50, p = 0.215), (ii) stage III vs. I (HR 5.11, p = 0.025), and (iii) stage IV vs. I (HR 10.3, p = 0.003) and PFS: (i) stage II vs. I (HR 2.21, p = 0.005), (ii) stage III vs. I (HR 4.57, p < 0.001), and (iii) stage IV vs. I (HR 9.48, p < 0.001). Conclusion The new R-ISS/PET had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely. Thus, R-ISS/PET is applicable for identifying heterogeneous manifestation of clinical MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Various nonincisional techniques for double eyelid surgery have been introduced in the past. They are simple, noninvasive, and efficient techniques to create a double eyelid. The authors prefer the full-thickness single continuous method using the 7-0 nylon, round long needle. Appropriate choice of the patients and surgical method results in a natural, esthetically pleasing eyelid and decreases the loss of eyelid crease.

Venous thromboembolism (VTE) may lead to diminished quality of life and ultimately worse prognosis in cancer patients, but there is limited data on the incidence, risk factors and mortality impact of VTE in Asian primary central nervous system lymphoma (PCNSL) patients.To report the incidence, risk factors and mortality impact of VTE in Asian PCNSL patients.From 7 academic centers in Korea, 235 newly diagnosed PCNSL patients undergoing chemotherapy were retrospectively identified during period of January 2004 to September 2018.All patients but 12 (6 T-cell, 6 other B-cell) had diffuse large B-cell lymphoma. During the median follow-up of 21 months, 33 patient (14.0%) developed VTE. Of the VTE events, 11 (33.3%) were deep vein thrombosis (DVT), 15 (45.5%) were pulmonary thromboembolism (PTE), and 7 (21.2%) were DVT with PTE. The median time to VTE was 2 months and the one-year actuarial incidence was 11.7%. On multivariate analysis, ECOG performance ≥2, age60 years, female sex, and Hb10 g/dL were independently associated with VTE. The patients with VTE were associated with shorter disease specific survival (P = 0.046) and overall survival (P = 0.022).Overall, the incidence of VTE in Asian PCNSL seems to be lower compared to Western population. As VTE development is associated with overall survival and indicative of relapse, careful close monitoring is warranted.

OBJECTIVES Posterior ventricular anchoring neochordal (PVAN) repair is a non-resectional technique for correcting mitral regurgitation (MR) due to posterior leaflet prolapse, utilizing a single suture anchored in the myocardium behind the leaflet. This technique has demonstrated clinical efficacy, although a theoretical limitation is stability of the anchoring suture. We hypothesize that the PVAN suture positions the leaflet for coaptation, after which forces are distributed evenly with low repair suture forces. METHODS Porcine mitral valves were mounted in a 3-dimensional-printed heart simulator and chordal forces, haemodynamics and echocardiography were collected at baseline, after inducing MR by severing chordae, and after PVAN repair. Repair suture forces were measured with a force-sensing post positioned to mimic in vivo suture placement. Forces required to pull the myocardial suture free were also determined. RESULTS Relative primary and secondary chordae forces on both leaflets were elevated during prolapse (P DISCUSSION PVAN repair eliminates MR by positioning the posterior leaflet for coaptation, distributing forces throughout the valve. Given extremely low measured forces, the strength of the repair suture and the myocardium is not a limitation.

Objective: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). Methods: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. Results: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT p = 0.010) and prior platelet transfusion p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. Conclusion: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n = 129 (67.9%); VTD6, n = 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P 2-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P = 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P = 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.

이태준의 단편소설들은 일본의 식민지 정책 때문에 몰락하여 고향을 떠나는 조선 농민들, 1930년대 경성 시내와 변두리 지역에 거주하는 가난한 조선인들을 주로 묘사하였다. 이태준 단편소설에 관한 기존의 연구는, ‘일본은 근대 그리고 조선은 전근대적인 것’이라는 관점에서 그의 소설이 근대화로 사라져가는 조선적인 것에 향수를 보인다고 주장했다. 반면에 이 논문은 이태준이 묘사한 조선인의 모습은 식민지 근대화 때문에 새롭게 생겨난 것이라고 보았다. 이태준은 일본 제국과 식민지 조선의 국제 분업에 의한 조선의 불균등 발전과 그로 인해 생긴 새로운 유형의 조선인과 그 삶을 묘사하였다. 제국은 하층 조선인들을 특별히 보호하지 않아도 사라지지 않는 존재인 잉여 노동력으로 보았다. 이에 반해, 이태준은 자신의 소설에서 이들을 아름답고 섬세한 조선어로 묘사함으로써 가치가 있는 것으로 만들었다. 한마디로, 이태준의 단편소설은 하층 조선인을 묘사함으로써 식민통치자에는 아무런 가치가 없었던 그들에게 예술적인 가치를 부여하였으며, 이런 방식으로 ‘식민지 모더니즘’의 한 유형을 창조하였다.

Although radiotherapy has been successfully applied to treat many cancer types, surviving cancer cells often acquire therapeutic resistance, leading to increased risk of local recurrence and distant metastases via modification of the tumor microenvironment. Previously, we reported that high expression of Bcl-w in cancer patients is significantly correlated with poor survival as well as malignant activity. However, the relationship between ionizing radiation (IR)-induced resistance and Bcl-w expression in cancer cells is currently unclear. We showed that IR-induced Bcl-w contributes to EMT (epithelial-mesenchymal transition), migration, angiogenesis, stemness maintenance, and metastasis by promoting the expression of factors related to these phenotypes, both in vitro and in vivo. Meanwhile, IR enhanced hypermethylation of miR-205-5p CpG islands through Src activation, leading to decreased miR-205-5p expression and, in turn, potentially stimulating Bcl-w-mediated malignant activity and metastasis. The clinical applicability of Bcl-w and miR-205-5p from cells or animal models was confirmed using tissues and plasma of breast carcinoma patients. Based on the collective findings, we propose that miR-205-5ps as important negative mediators of resistance in radiotherapy could serve as useful potential targets of concurrently applied genetic therapy aimed to inhibit tumor aggressiveness and enhance the efficiency of radiotherapy in cancer patients. Keywords: radioresistance, Bcl-w, miR-205-5p, hypermethylation, metastasis

Ultra-deep sequencing detects low-frequency genetic mutations with high sensitivity. We used this approach to prospectively examine mutations in the BCR/ABL1 tyrosine kinase from patients with newly diagnosed, chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor nilotinib. Between May 2013 and November 2014, 50 patients from 18 institutions were enrolled in the study. We screened 103 somatic mutations and found that mutations in the P-loop domain were the most frequent (173/454 mutations in the P-loop) and noted the presence of the V299 L mutation (dasatinib-resistant/nilotinib-sensitive) in 98 % of patients (49/50). No patients had Y253H, E255 V, or F359 V/C/I mutations, which would recommend dasatinib rather than nilotinib treatment. The S417Y mutation was associated with lower achievement of a major molecular response (MMR) at 6 months, and the V371A mutation was associated with reduced MMR and MR4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P=0.039; MR4.5 for 15 months: 94.1 % vs. 25 %, P=0.002). Patients with known nilotinib-resistant mutations had lower rates of MR4.5 achievement. In conclusion, ultra-deep sequencing is a sensitive method for genetic-based treatment decisions. Based on the results of these mutational analyses, nilotinib treatment is a promising option for Korean patients with CML.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (&ge, 70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4&ndash, 47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3&ndash, 5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.

Given the unsatisfactory survival in patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for peripheral T-cell lymphomas (PTCLs), we conducted a prospective trial of busulfan (Bu), etoposide (E), cytarabine (A), and melphalan (M) (BuEAM), including IV Bu instead of carmustine (BCNU) as in standard BEAM, as a high-dose regimen in such patients. This study evaluated the efficacy and toxicity of BuEAM as a high-dose regimen for ASCT in patients with T-cell lymphomas. The high-dose chemotherapy at seven centers in Korea included Bu (3.2 mg/kg IV qd from day 6 to day 5), E (200 mg/m2 IV bid on day 4 and day 3), A (1 g/m2 IV qd on day 4 and day 3), and M (140 mg/m2 IV qd on day 2). Eighty-one patients were enrolled in this study. The main subtypes were peripheral T-cell lymphoma, not other specified (n = 32, 39.5%), NK/T-cell lymphoma (n = 22, 27.5%), and angioimmunoblastic T-cell lymphoma (n = 12, 14.8%). Upfront and salvage ASCTs were performed in 65 (80.2%) and 16 (19.8%) patients, respectively. The disease status of the patients before ASCT was 54 patients (66.7%) with complete response and 27 patients (33.3%) with partial response. The common grade-III toxicities were anorexia (8.6%), diarrhea (7.4%), and stomatitis (4.9%). No veno-occlusive disorder was noted. Fifty-six (69.1%) and seven (8.6%) patients achieved complete and partial response, respectively, after ASCT, although 17 patients (21.0%) showed progressive disease. At a median follow-up duration of 49.3 months, the estimated 3-year progression-free survival and overall survival were 55.2% and 68.2% in all patients. The BuEAM high-dose regimen for ASCT was well tolerated and seemed to be effective in patients with T-cell lymphomas.

In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic ab normalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined ac cordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.

Background/Aims This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. Conclusions For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Augmented reality (AR) systems have been proposed for medical needle procedures as alternatives to restore the physician's natural perspective and head motion parallax that are lost when using standard imaging methods. AR systems have assumed a rigid needle, but in practice, a needle can experience large deflections that can lead to significant errors. We combine an instrumented needle that measures bending deflections with optical tracking of the needle base for precision and an AR system to provide users with precise three-dimensional rendering of needle motion and deflection inside a body. In controlled tests, users guided a needle through 7 cm of tissue phantom to reach a 2-mm diameter target. We found that displaying needle shape allows users significantly reduce placement errors when compared to the rigid needle assumption. In addition, a new display technique called tip tangent extrapolation, based on the sensed needle endpoint and direction, allowed users to further reduce errors resulting in 26% less error when compared to a rigid needle assumption.

Predictive factors for initiating hypomethylating agents’ (HMAs) treatment and the survival benefit of HMAs for lower-risk myelodysplastic syndrome (LR-MDS) are still unknown. This study evaluated the factors affecting the use of HMAs and compared long-term outcomes between best supportive care (BSC) and HMA groups after matching baseline clinical factors. Data of 353 patients diagnosed with LR-MDS by International Prognostic Scoring System between October 1992 and July 2013 were retrospectively analyzed. HMAs were administered continuously until a clinical response or progression. HMAs were administered to 243 patients with median 45 days (range 0–7078 days) after diagnosis, while 110 patients were treated with BSC. HMAs were administered over a median of 5 cycles and overall response was achieved in 104 patients (42.8%). The cumulative incidence of HMA treatment increased in higher-risk groups by other risk scoring systems. Three-year overall survival (OS) rate was higher in BSC group (69.1%) than HMA responders (47.4%, p = 0.065) or HMA non-responders (46.3%, p = 0.005). Among 162 case-matched cohorts, 3-year OS rates were comparable between the BSC group (67.1%) and HMA responders (58.1%, p = 0.914), while that of HMA non-responder was low (32.2%, p

Background Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk. Methods Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables. Results 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0–8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups. Conclusions This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle. Clinical Trial Id WHO ICTRP number, KCT0001071

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4, and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. Methods: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. Results: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015–4.842; p = 0.0458). Conclusion: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

Purpose We compared two induction regimens, idarubicin (12 mg/m2/d for 3 days) versus high-dose daunorubicin (90 mg/m2/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m2/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.

// 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.

// Eun Sook Kim 1, * , Young Eun Choi 1, * , Su Jin Hwang 1 , Young-Hoon Han 1 , Myung-Jin Park 1 , In Hwa Bae 1 1 Division of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: In Hwa Bae, email: ihbae@kirams.re.kr Keywords: radiation, interleukin-4, miR-340/429, tumorigenicity, metastasis Received: August 10, 2016 Accepted: November 07, 2016 Published: November 24, 2016 ABSTRACT Radiotherapy induces the production of cytokines, thereby increasing aggressive tumor behavior. This radiation effect results in the failure of radiotherapy and increases the mortality rate in patients. We found that interleukin-4 (IL-4) and IL-4Rα (IL-4 receptor) are highly expressed in various human cancer cells subsequent to radiation treatment. In addition, IL-4 is highly overexpressed in metastatic carcinoma tissues compared with infiltrating carcinoma tissues. High expression of IL-4 in patients with cancer is strongly correlated with poor survival. The results of this study suggest that radiation-induced IL-4 contributes to tumor progression and metastasis. Radiation-induced IL-4 was associated with tumorigenicity and metastasis. IL-4 expression was downregulated by miR-340 and miR-429, which were decreased by ionizing radiation (IR). Radiation-regulated miR-340/429-IL4 signaling increased tumorigenesis and metastasis by inducing the production of Sox2, Vimentin, VEGF, Ang2, and MMP-2/9 via activating JAK, JNK, β-catenin, and Stat6 in vitro and in vivo . Our study presents a conceptual advance in our understanding of the modification of tumor microenvironment by radiation and suggests that combining radiotherapy with genetic therapy to inhibit IL-4 may be a promising strategy for preventing post-radiation recurrence and metastasis in patients.

// 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.

Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, single-suture technique for correcting posterior leaflet prolapse. While this technique has demonstrated clinical efficacy, a possible limitation is the stability of the suture anchored into myocardium as opposed to the fibrous portion of a papillary muscle. Hypothesis: We hypothesize that the PVAN suture serves only to position the leaflet for coaptation, after which systolic forces will be distributed throughout the valve, resulting in low peak forces on the suture. Methods: A left heart simulator was constructed using 3D printing, tuned to generate physiological pressure and flow waveforms, then validated. Porcine mitral valves (n=9) were dissected and mounted within the simulator. Chordal forces were measured using Fiber Bragg Grating (FBG) sensors, sewn in place using PTFE suture. FBG sensors are strain gauges made of 125 μ m optical fibers that use reflected peak wavelength changes to measure strain. Hemodynamic and echocardiographic data were also collected. Isolated severe mitral regurgitation (MR) was induced by cutting P2 primary chordae. The valve was repaired using the PVAN technique, anchoring the suture to a customized force-sensing post positioned to mimic in vivo placement. Results: Forces on 1° and 2° chordae of both anterior and posterior leaflets were significantly elevated in the prolapse condition ( P < 0.05). PVAN resulted in elimination of MR in all valves, as well as normalization of chordae forces to baseline levels for posterior primary ( P < 0.01 ) , posterior secondary ( P < 0.01 ) , and anterior primary chordae ( P < 0.05 ) , with reduction in anterior secondary chordal forces approaching significance ( P = 0.055 ) . Peak forces on the PVAN stitch were minimal, even compared to the forces experienced by primary chordae of normal, healthy valves ( P < 0.05). Conclusions: The PVAN technique eliminates MR by effectively positioning the posterior leaflet for optimal coaptation, distributing the forces amongst the subvalvular apparatus. Given the extremely low forces involved, the strength of the ventricular anchoring suture and myocardial anchoring point should not be a limiting factor.

Background Neochordoplasty is an important repair technique, but optimal anchoring position is unknown. Although typically anchored at papillary muscles, new percutaneous devices anchor the neochordae at or near the ventricular apex, which may have an effect on chordal forces and the long-term durability of the repair. Methods Porcine mitral valves (n = 6) were mounted in a left heart simulator that generates physiologic pressure and flow through the valves, and chordal forces were measured with Fiber Bragg Grating strain gauge sensors. Isolated mitral regurgitation was induced by cutting P2 primary chordae, and the regurgitant valve was repaired with polytetrafluoroethylene neochord with apical anchoring, followed by papillary muscle fixation for comparison. In both situations, the neochord was anchored to a customized force-sensing post positioned to mimic the relevant in vivo placement. Results Echocardiographic and hemodynamic data confirmed that the repairs restored physiologic hemodynamics. Forces on the chordae and neochord were lower for papillary fixation than for the apical fixation (p = 0.003). In addition, the maximum rate of change of force on the chordae and neochordae was higher for apical fixation than for papillary fixation (p = 0.028). Conclusions Apical neochord anchoring results in effective repair of mitral regurgitation, albeit with somewhat higher forces on the chordae and neochord suture, as well as an increased rate of loading on the neochord compared with the papillary muscle fixation. These results may guide strategies to reduce stresses on neochordae as well as aid optimal patient selection.

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.

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.

A steering wheel modified to produce lateral skin stretch provides perceptible cues in a vehicle being driven on the road. We conducted tests to determine whether drivers can correctly perceive and react to skin stretch navigation cues. Additionally, we compare skin stretch feedback to audio navigation cues during an auditory N-back distraction task simulating a phone call. Results show a statistically significant difference (p-value = 0.044) between haptic (98.5%) and audio feedback (96.6%) in navigation accuracy and in N-back response accuracy (haptic = 89.9%, audio = 87.2%, p-value = 0.047).

Nanoparticles (NPs) have been widely utilized in the food industry as additives with their beneficial characteristics, such as improving sensory property and processing suitability, enhancing functional and nutritional values, and extending shelf-life of foods. Silica is used as an anti-caking agent to improve flow property of powered ingredients and as a carrier for flavors or active compounds in food. Along with the rapid development of nanotechnology, the sizes of silica fall into nanoscale, thereby raising concerns about the potential toxicity of nano-sized silica materials. There have been a number of studies carried out to investigate possible adverse effects of NPs on the gastrointestinal tract. The interactions between NPs and surrounding food matrices should be also taken into account since the interactions can affect their bioavailability, efficacy, and toxicity. In the present study, we investigated the interactions between food additive silica NPs and food matrices, such as saccharides, proteins, lipids, and minerals. Quantitative analysis was performed to determine food component-NP corona using HPLC, fluorescence quenching, GC-MS, and ICP-AES. The results demonstrate that zeta potential and hydrodynamic radius of silica NPs changed in the presence of all food matrices, but their solubility was not affected. However, quantitative analysis on the interactions revealed that a small portion of food matrices interacted with silica NPs and the interactions were highly dependent on the type of food component. Moreover, minor nutrients could also affect the interactions, as evidenced by higher NP interaction with honey rather than with a simple sugar mixture containing an equivalent amount of fructose, glucose, sucrose, and maltose. These findings provide fundamental information to extend our understanding about the interactions between silica NPs and food components and to predict the interaction effect on the safety aspects of food-grade NPs.

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.