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Objective: Bone marrow (BM) examinations are performed to evaluate hematological abnormalities. Focusing on patients with cytopenia, we aimed to determine the circumstances under which a BM examination can assist in the diagnosis of hematologic diseases.Methods: The medical records of 738 patients who underwent BM examination from March 2011 to March 2019 at Soonchunhyang University Seoul Hospital were reviewed. In total, 234 patients underwent a BM examination to identify the cause of cytopenia. Excluded from the analysis were BM examinations performed to diagnose specific diseases and evaluate disease status.Results: Results suggesting suboptimal outcome (n=6) or BM invasion of solid tumors (n=13) were excluded. Immune thrombocytopenic purpura patients (n=52) with normal BM examination results were also excluded. One hundred sixty-three patients who underwent BM examination to determine the cause of cytopenia were included in the analysis. A comparison of non-specific results (n=56) to those pointing to an underlying hematologic disease (n=107) showed that patients with severe neutropenia or severe thrombocytopenia were more likely to be diagnosed with a hematologic disease. Specifically, as the number of severe cytopenias increased, the likelihood of a hematologic disease diagnosis was significantly augmented. Patients with end-stage renal disease, autoimmune disease, or liver cirrhosis were more likely to receive non-specific results.Conclusion: In conclusion, seeking the underlying disease or drug should be a primary target for patients with cytopenia. In cases of severe cytopenia in more than one lineage, BM examination should be strongly considered to diagnose an underlying hematologic disease.

Chronic inflammation plays a critical role in the pathogenesis of myeloproliferative neoplasm (MPN), and inflammatory conditions are closely related to the development and exacerbation of atherosclerosis. This study aimed to compare carotid plaque burden and neutrophil-lymphocyte ratio (NLR) in the essential thrombocythemia (ET)/polycythemia vera (PV) and control groups.We retrospectively assessed carotid plaque burden and NLR in patients with ET/PV between January 2010 and September 2021 and propensity-score matched these patients to control subjects from the general population. All patients underwent carotid imaging using carotid ultrasonography for atherosclerosis screening. After 3:1 propensity-score matching, 140 patients in the control group were matched to 51 patients in ET/PV group. The mean NLR was significantly higher in the MPN group than in the control group (4.77 ± 3.96 vs. 1.93 ± 1.03, p 0.001). The carotid plaque score was also higher in MPN group than in the control group (2.37 ± 1.47 vs. 1.94 ± 1.17, p = 0.038).Patients with PV/ET show a higher NLR and carotid plaque burden than the normal population. This reflected that PV/ET was a highly inflammatory and atherosclerotic condition expressing potentially increased cardiovascular risk.

Objective: Eosinophilia in patients on hemodialysis has already been reported. It has been associated with allergy to dialyzers and exaggerated activation of complement during hemodialysis. Its etiology, however, remains unknown. In addition, there are not enough studies on eosinophilia in patients on hemodialysis in Korea. Therefore, we performed this retrospective study to find out the prevalence and possible etiologic factors of blood eosinophilia in patients undergoing hemodialysis.Methods: Between January 2013 to December 2015, the patients hospitalized for hemodialysis at Soonchunhyang University Hospital and National Health Insurance Service Medical Center (Ilsan Hospital) were included in this study. Eosinophilia was defined when absolute eosinophil count was greater than 500/μL, respectively. We retrospectively reviewed the medical records of patients about parasite infection, other malignancies, and history of kidney transplantation.Results: Of the 2,155 patients hospitalized for hemodialysis at two centers, 1,057 patients (49%) were found to have eosinophilia. We investigated 1,199 patients’ information (Soonchunhyang University Hospital) by the medical records. Two hundred two patients (16.8%) had no identifiable and/or possible causes. Only two patients complained of symptoms such as itching. Steroids were administered to control symptoms, and both patients had normal eosinophil levels, and steroids were discontinued. Other patients did not complain of specific symptoms associated with eosinophilia and did not take medication such as steroids. Eosinophilia was improved in 49% of patients without special treatments.Conclusion: We found that the eosinophil counts in patients with end stage renal disease on hemodialysis were frequently elevated. However, in most cases, eosinophilia was not clinically relevant.

ESG(Environment, Social, Governance)는 기업의 친환경에 대한 책임, 사회적 책임 경영, 건전한 지배구조 개선 등 투명한 경영을 고려하여야 지속 가능한 발전을 할 수 있다는 의미로, 국내뿐만 아니라 전 세계적으로 큰 화두가 되고 있는 주제이다. ESG의 요소 중 환경요소(E)는 사회요소(S)나 지배구조요소(G)에 비하여 상대적으로 계량화 및 사후관리가 쉽다는 특징이 있고, 환경요소(E)에 대한 계량화 및 사후관리는 회계적 측면과 세법적 측면에서 고려하여 볼 때 그 해결책을 모색할 수 있을 것으로 생각된다. 본 연구는 ESG의 환경요소(E)와 관련하여 회계적 측면의 정보 공시기준과 세법적 측면의 관련 법 규정을 검토하여 보고, 회계와 세법의 연관관계를 고려한 제도적 개선방안을 제안하는 것을 목적으로 한다. 우리나라의 경우 아직 ESG의 환경요소(E) 관련 정보 공시가 의무화되어 있지 않은 단계여서 기업의 자율적인 공시가 이루어지고 있고, 여러 근거 규정에 따라 다른 방법으로 공시함에 따라 환경요소(E) 정보 공시기준의 일관성이 결여되어 있다. 정보의 공시 의무대상을 확대하여 ESG 정보 공시를 강화할 수 있도록 관련 제도를 보완할 필요가 있다. ESG 관련 정보를 공시하는 방법과 관련된 비용과 효익을 검토하여 보다 효율적인 방법으로 일원화하여 규정하는 것이 바람직할 것이다. 제도적으로 의무화하여 공시된 환경요소(E) 관련 정보의 활용가능성을 높이기 위해서는 관련 정보의 수요자인 투자자들의 필요 정보에 대한 접근가능성을 높이는 것이 필수적일 것이다. 정보 공시기준의 비교가능성을 제고하기 위해서는 유용한 재무적 보고의 전제인 효익과 비용을 고려하여 환경요소(E) 정보 공시 항목에 대한 구체적인 지침을 마련할 필요가 있다. 이때 관련 정보를 투자의사결정에 활용하는 투자자의 의견을 수렴하여 반영함으로써 정보 공시의 효과를 극대화할 수 있을 것이고, 보다 많은 투자자들이 필요로 하는 정보 공시 항목을 우선적으로 공시하고 그 범위를 점진적으로 확대하는 방안을 고려할 필요가 있다. 정부의 ESG 정책은 기업의 투자계획과 그에 따른 세제지원을 고려한 기업의 조세계획에 영향을 미칠 수 있으므로 세법적 측면에서 활용될 수 있는 환경요소(E) 관련 세부지표를 마련한다면 보다 실효성 높은 자료가 될 것이다. 단순히 과거에 발생한 사실을 공시하는 것이 아니라, 환경요소(E)와 관련된 위험 또는 기회 요소 등을 포함하여 공시하는 방안을 고려해 볼 수 있다. 기후 변화와 관련된 위험 및 기회를 평가하고, 이를 관리하기 위한 지표와 동시에 감축 목표를 공개하도록 하는 TCFD(Task Force on Climate-related Financial Disclosures, 기후 변화와 관련된 재무 정보 공개를 위한 태스크포스)의 권고안은 환경요소(E)를 고려하여 기업의 장기적 가치를 평가할 수 있도록 하는 참고할 만한 지표가 될 것으로 사료된다. 환경요소(E)와 관련하여 공시된 정보가 보다 의미 있고 유용하게 활용되기 위해서는 관련 정보에 대한 신뢰성을 제고할 수 있는 방안을 마련하는 것 또한 중요하다. 환경보호를 주관하는 환경부와의 긴밀한 협력체제를 구축하여 환경 관련 전문가들이 환경요소(E) 관련 공시 정보를 검증하도록 하는 시스템을 구축하는 방안을 고려해 볼 수 있다. 현행의 교통·에너지·환경세법, 지방세법, 개별소비세법 등에 흩어져 있는 환경 관련 세제를 환경세법에서 일목요연하게 규정하고, 실질적으로 조세의 성격을 갖는 부담금을 환경세법에서 통합하여 입법할 필요가 있다. 환경세를 입법함에 있어서 중요한 문제는 실증분석을 통하여 외부효과로 인한 사회적 비용을 제거할 수 있는 수준의 세율을 설정하는 것이다. 우리나라의 장기적인 환경 정책상 온실가스의 감축 목표를 정하고 이를 달성하기 위하여 필요한 수준의 실질적인 세율을 우선적으로 결정하고, 초기 단계에서는 낮을 세율을 적용하다가 점진적으로 실질적인 세율로 상향하는 것이 기존의 법 체계를 환경세법으로 성공적으로 전환하는 현실적이고도 효과적인 방법이 될 것이다. 환경오염을 감소시키는 정책과 상응하는 과세제도를 구축하기 위해서 탄소의 함량이 높은 유연탄에 대하여는 높은 세율로, 탄소의 함량이 낮은 무연탄에 대하여는 낮은 세율로 과세하고, 자동차 주행에 대한 자동차세는 배기량 기준이 아닌 이산화탄소 배출량을 기준으로 차등하여 과세하여야 할 것이다. 환경세로 확보된 세수는 에너지의 효율을 높일 수 있는 기술을 개발하고 환경오염을 감소시키고 친환경산업을 육성할 수 있는 재원으로 사용될 수 있도록 하여야 하고, 환경세의 역진성을 완화하기 위한 방안도 고려할 필요가 있다. 에너지절약 시설과 환경보전 시설에 대하여 다른 일반 사업용 유형자산과 동일한 세액공제율을 적용하는 현행 규정으로는 에너지를 효율적으로 사용하고 환경을 보전하기 위한 정책효과를 거두기 어렵다고 생각한다. 에너지절약 시설과 환경보전 시설 등을 포함하는 ‘친환경 관련 투자액’의 범위에 대한 새로운 검토가 필요하고, ‘친환경 관련 투자액’에 대하여는 세액공제율을 상향 조정할 필요가 있다. 환경보전 시설에 대한 세액공제 규정은 개인의 경우 사업소득이 있는 경우로만 한정하고 있는데, 사업소득이 있지 아니한 개인의 경우에도 재활용 시설 등의 환경보전 시설을 설치할 수 있는 바, 세액공제를 사업소득에 대한 소득세로만 한정하는 규정은 삭제하는 것이 바람직하다. 친환경건축물인증 또는 에너지효율등급인증을 받은 건축물뿐만 아니라 ‘친환경 건축물 등’에 대하여는 가속감가상각을 할 수 있도록 법인세법과 소득세법의 감가상각 방법 규정을 개정할 필요가 있다. ESG의 환경요소(E) 관련 조세지원제도를 설계함에 있어서 정보 공시기준과 연계하여 법인세법, 소득세법, 조세특례제한법 등을 규정하는 방안이 보다 효과적일 것이라고 생각한다. 본 연구는 ESG의 환경요소(E)에 초점을 맞추어 회계와 세법의 연관관계를 고려하여 정보공시기준 및 세법 규정을 종합적으로 검토하고 문제점을 분석함과 동시에 제도적 개선방안을 제시하였다는 점에서 큰 의미가 있다고 생각된다.

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.

Background The global TARGET survey examined real-world management of chronic myeloid leukemia (CML) compared with international guideline recommendations. This report focused on the responses of physicians from South Korea compared with those of physicians from the rest of the world (ROW). Methods The self-administered, online survey, comprising 23 questions and clinical case scenarios, was completed between April and August 2017. It was designed to gather information on practicing physicians and local practices for CML diagnosis, disease monitoring, treatment, and adverse event (AE) management. Results While there were similarities in the mutation analysis and treatment efficacy between Korea and the ROW, there were also differences in CML management. Initial diagnostic testing was more comprehensive in Korea than in the ROW, and there was significantly better access to standardized polymerase chain reaction testing. Assessment of BCR-ABL levels during the first 12 months of treatment was excellent in Korea, and there was greater frontline use of second-generation BCR-ABL tyrosine kinase inhibitors. Korean physicians were significantly less likely to switch therapy for hematologic AEs. Treatment-free remission was not an important goal of therapy among Korean or ROW physicians. Conclusion This study identified some differences in the current CML management between Korea and the ROW; CML management in Korean patients was generally in line with the current guidelines.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.

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.

Purpose High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL.Materials and Methods Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS).Results Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation.Conclusion There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host–microbiome crosstalk in IDA.

Genetic differences may be associated with the response to tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). In this study, we identified genetic alterations between rapid and slow responders (BCR/ABL1 International Scale at 6 months: ≤0.1 % vs. 0.1 %) of TKI treatment in chronic phase CML patients. Our analyses involved single nucleotide polymorphism (SNP), a Genome Wide Association Study and a Network-wide Association Study (NetWAS). Seventy-two patients from 16 institutions were enrolled and treated with a TKI, nilotinib. Gene Set Analysis identified genetic alterations in pathways related to the differentiation, proliferation, and activity of various innate immune cells. The NetWAS analysis found that genes associated with natural killer (NK) cells (PTPRCAP, BLNK, HCK, ARHGEF11, GPR183, TRPV2, SHKBP1, CD2) showed significant differences between rapid and slow responders of nilotinib. However, we found no significantly different genetic alterations according to the response in the SNP analysis. In conclusion, we found that rapidity of response to TKI was associated with pathway-associated genetic alterations in immune cells, particularly with respect to NK cell activity. These results suggested that the innate immune system at initial diagnosis had an important role in treatment response in patients with CML.

Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN–next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).

Background/aims Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. Methods In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. Results Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. Conclusion Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

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.

Purpose: This study utilizes the KNV measure to evaluate performance of national pension funds of Korea. Design/methodology/approach: First, this study investigates whether fund managers pick stocks in expansions and time the market in recessions. Second, we examine skilled funds that have both high picking skill in booms and high timing skill in recessions. Third, we examine whether skilled managers have timing ability as well as picking ability. Finally, persistence of skill indexes is investigated. Findings: First, market timing skill is more relevant in recessions whereas stock selection skill is more relevant in expansions. Second, the performance differences between superior and inferior funds are persistent over one-year. Finally, there is no evidence that the same fund managers who display superior stock picking skill in expansions show superior market timing skill in recessions. Research limitations/implications: Since no institutions or organizations provide real-time indicators of the business cycle, switching strategy between timing and picking is not available. Originality/value: This is the first research to analyze the national pension fund using KNV methodology in the Korean market.

DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R2 = 0.74, P RUNX1-RUNX1T1 and cKIT-D816mut at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P RUNX1-RUNX1T1 AML.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRD

Background/Aims: A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe tox icities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary compli cations in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. Methods: We retrospectively reviewed the medical records and chest image find ings of 644 patients who were treated with targeted antineoplastic agents at Soon chunhyang University Hospital between May 2005 and September 2014. Results: Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontin ued in all patients, while 11 patients were simultaneously treated with glucocorti coids. Three patients died of drug-related pulmonary toxicity. Conclusions: During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontin uing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.

Aim Cytotoxic chemotherapy-based treatment of multiple myeloma (MM) is not curative, and the disease eventually recurs. This is partially because although currently available anti-MM strategies are effective in targeting the bulk of tumor cells, they do not target the tumor-initiating subpopulation of cancer stem cells. This study investigated the prevalence and biological functions of side population (SP) cells in MM cell lines including RPMI8226, ARH77, MM.1R and IM 9. Materials and methods Flow cytometry-based Hoechst 33342 staining was used to evaluate the existence of SP cells. In addition, the ability of SP cells to regenerate the original population was determined. Results The frequency of SP cells was heterogeneous. Most cell lines (ARH77, IM9, and MM.1R) contained fewer than 1% SP cells; however, RPMI8226 contained approximately 10% SP cells. Sorted SP cells showed a higher proliferative ability and clonogenicity than the MP in the RPMI8226 myeloma cell line. The activity of ATP-binding cassette subfamily G member 2 (ABCG2), which is associated with high rates of proliferation, was higher in SP cells. However, the expression of specific surface markers such as cluster of differentiation (CD)138, CD34, CD38, CD19, CD20, and CD27 did not differ between SP and MP cells. Bortezomib was the only agent that significantly affected proliferation of both SP and MP cells. Conclusion Our studies demonstrated that the SP fraction of myeloma cells possessed clonogenic tumor-initiating potential and revealed new mechanisms of action for bortezomib on SP cells.

Purpose Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and methods This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed. Results Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naive patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common. Conclusion Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naive benefitted from dovitinib.

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.