Publications by authors named "Young-Shin Lee"

92 Publications

Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation.

J Korean Med Sci 2021 Jun 14;36(23):e151. Epub 2021 Jun 14.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR).

Methods: We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000-September 2017) at our center.

Results: Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97-28.0, < 0.001) and lower CD34⁺ cell dose (RR, 2.44-2.84, = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse.

Conclusion: Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.
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http://dx.doi.org/10.3346/jkms.2021.36.e151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203852PMC
June 2021

Characteristics of electronic cigarette user and traditional smokers: 2017 Youth risk behavior surveillance system.

Public Health Nurs 2021 Jun 8. Epub 2021 Jun 8.

School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Although electronic cigarette (e-cigarette) use among adolescents rapidly has increased over the past decade, which has raised concerns over the corresponding behavioral health risks, the current literature presents limited data for understanding the characteristics of adolescent e-cigarette users.

Objective: The purpose of this study was to (1) identify general characteristics that may be shared between e-cigarette users and traditional cigarette smokers and (2) examine the unique characteristics of e-cigarette users vis-à-vis traditional cigarette smokers.

Design: Cross-sectional descriptive study.

Sample And Data Source: A total of 14,765 9th- to 12-grade students drawn from the CDC 2017 Youth Risk Behavior Surveillance System.

Results: We observed that the prevalence of marijuana, alcohol, and other illicit drug use was higher among e-cigarette users and traditional tobacco users than non-users. Moreover, physically active adolescents were more likely to use e-cigarettes than those who were physically inactive, although the level of the activity did not predict smoking status.

Conclusion: We recommend that primary prevention strategies for e-cigarette use should be incorporated in physical education programs and target adolescents who engage in not only health risk behaviors, but also health promoting behaviors, such as physical activity.
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http://dx.doi.org/10.1111/phn.12936DOI Listing
June 2021

Validation of Adhesive Single-Lead ECG Device Compared with Holter Monitoring among Non-Atrial Fibrillation Patients.

Sensors (Basel) 2021 Apr 30;21(9). Epub 2021 Apr 30.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

There are few reports on head-to-head comparisons of electrocardiogram (ECG) monitoring between adhesive single-lead and Holter devices for arrhythmias other than atrial fibrillation (AF). This study aimed to compare 24 h ECG monitoring between the two devices in patients with general arrhythmia. Twenty-nine non-AF patients with a workup of pre-diagnosed arrhythmias or suspicious arrhythmic episodes were evaluated. Each participant wore both devices simultaneously, and the cardiac rhythm was monitored for 24 h. Selective ECG parameters were compared between the two devices. Two cardiologists independently compared the diagnoses of each device. The two most frequent monitoring indications were workup of premature atrial contractions (41.4%) and suspicious arrhythmia-related symptoms (37.9%). The single-lead device had a higher noise burden than the Holter device (0.04 ± 0.05% vs. 0.01 ± 0.01%, = 0.024). The number of total QRS complexes, ventricular ectopic beats, and supraventricular ectopic beats showed an excellent degree of agreement between the two devices (intraclass correlation coefficients = 0.991, 1.000, and 0.987, respectively). In addition, the minimum/average/maximum heart rates showed an excellent degree of agreement. The two cardiologists made coherent diagnoses for all 29 participants using both monitoring methods. In conclusion, the single-lead adhesive device could be an acceptable alternative for ambulatory ECG monitoring in patients with general arrhythmia.
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http://dx.doi.org/10.3390/s21093122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124998PMC
April 2021

An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells.

PLoS One 2021 1;16(4):e0248870. Epub 2021 Apr 1.

Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Republic of Korea.

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248870PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016313PMC
April 2021

Second allogeneic hematopoietic stem cell transplantation in patients with acute leukemia relapsed after allogeneic hematopoietic stem cell transplantation.

Clin Transplant 2021 Mar 3;35(3):e14199. Epub 2021 Jan 3.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

The prognosis of patients with acute leukemia relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) is dismal. We aimed to evaluate the outcomes and prognostic factors of the second HSCT (HSCT2) in acute leukemia patients relapsed after the first HSCT (HSCT1). We analyzed 80 patients who received HSCT2 for relapsed acute leukemia in two Korean institutes. All but four patients received HSCT2 from a donor other than matched sibling donor: an unrelated donor (URD) in 30 and a familial haploidentical donor (FHD) in 46. Forty-four patients (55.0%) were in complete remission (CR) or CR with incomplete count recovery (CRi) at HSCT2, and the median time from HSCT1 to relapse was 9 months. The 2-year overall survival (OS) and event-free survival (EFS) were 21.0% and 17.5%, respectively. The outcomes were similar between URD and FHD. Multivariate analysis demonstrated that disease status (active disease vs. CR/CRi) at HSCT2 and remission duration after HSCT1 were independent prognostic factors for OS and EFS after HSCT2. HSCT2 from URD or FHD was feasible in patients with acute leukemia relapsed after allogeneic HSCT. Also, our study confirmed two critical prognostic factors; disease status at HSCT2 and remission duration after HSCT1.
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http://dx.doi.org/10.1111/ctr.14199DOI Listing
March 2021

Role of Sevoflurane on Natural Killer Group 2, Member D-Mediated Immune Response in Non-Small-Cell Lung Cancer: An In Vitro Study.

Med Sci Monit 2020 Nov 3;26:e926395. Epub 2020 Nov 3.

Department of Anesthesia and Pain Medicine, Pusan National University, School of Medicine, Busan, South Korea.

BACKGROUND The purpose of this study was to investigate the effects of sevoflurane on cancer immunosurveillance and metastasis in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS NCI-H23 cells, a human NSCLC cell line, were incubated with or without sevoflurane at the concentrations of 0, 12.5, 25, 50, 100, and 200 μM for 6 h. Cell viability, the expression of natural killer group 2, member D ligands (NKG2D ligands: UL16-binding proteins 1-3 [ULBP1-3] and major histocompatibility complex class I chain-related molecules A/B [MICA/B]), the expression of matrix metalloproteinases (MMPs), NK cell-mediated cytotoxicity, and cancer cell migration were measured. RESULTS At 12.5, 25, 50, and 100 μM, sevoflurane increased the expression of NKG2D ligands (ULBP2-3 and MICA, ULBP1-3, ULBP1-3, and ULBP1, respectively). Sevoflurane decreased the expression of NKG2D ligands at 200 μM (MICA/B). NK cell-mediated lysis of NCI-H23 cells at 200 μM sevoflurane was significantly reduced compared with the control (P=0.025; target cell: effect cell=1: 10). Sevoflurane increased the expression of MMP-1, -2, and -9 and increased cell migration in NCI-H23 cells at 50, 100, and 200 μM (P=0.001, 0.035, and 0.039, respectively, compared with the control after 18 h of wound formation). CONCLUSIONS Sevoflurane could suppress NKG2D-mediated NK cell cytotoxicity and increased expression of MMPs and migration in NCI-H23 cells. Further research is needed to determine the effects of sevoflurane on cancer immunosurveillance and metastasis in NSCLC.
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http://dx.doi.org/10.12659/MSM.926395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648410PMC
November 2020

Culturally Congruent Health Care of COVID-19 in Minorities in the United States: A Clinical Practice Paper From the National Coalition of Ethnic Minority Nurse Associations.

J Transcult Nurs 2020 Sep;31(5):434-443

Nevada Health Centers, Las Vegas, NV, USA; President, National Coalition of Ethnic Minority Nurse Associations.

Race and ethnicity along with social determinants of health have been identified as risk factors for COVID-19. The purpose of this clinical paper is to provide an overview of the National Coalition of Ethnic Minority Nurse Associations (NCEMNA), present COVID-19 epidemiological data on five racial-ethnic groups, identify culturally congruent health care strategies for each group, and provide directions for practice and research. : NCEMNA collaborated to provide a clinical paper that addresses information about COVID-19 and culturally congruent health care in five racial-ethnic groups. : Every organization presented common themes across the different groups and unique perspectives that each group is faced with during this challenge. : This article provides an introduction to the issues that minority groups are facing. It is imperative that data are collected to determine the extent of the impact of COVID-19 in diverse communities in the country.
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http://dx.doi.org/10.1177/1043659620941578DOI Listing
September 2020

Potentiation of TRAIL‑induced cell death by nonsteroidal anti‑inflammatory drug in human hepatocellular carcinoma cells through the ER stress‑dependent autophagy pathway.

Oncol Rep 2020 Sep 25;44(3):1136-1148. Epub 2020 Jun 25.

Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 626‑870, Republic of Korea.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. The limited success with relapse of the disease in HCC therapy is frequently associated with the acquired resistance to anticancer drugs. To develop a strategy and design for overcoming the resistance of HCC cells to TNF‑related apoptosis inducing ligand (TRAIL)‑induced cell death, we evaluated the efficacy of a non‑steroidal anti‑inflammatory drug (NSAID) in combination with TRAIL against TRAIL‑resistant HCC cells expressing a high level of CD44. We revealed by MTT and western blotting, respectively, that celecoxib (CCB), an NSAID, and 2,5‑dimethyl celecoxib (DMC), a non‑cyclooxygenase (COX)‑2 inhibitor analog of CCB, were able to sensitize TRAIL‑resistant HCC cells to TRAIL, implicating a COX‑independent mechanism. CCB dose‑dependently enhanced LC3‑II and reduced p62 levels through AMPK activation and inhibition of the Akt/mTOR pathway and upregulated expression of ATF4/CHOP, leading to activation of endoplasmic reticulum (ER) stress‑dependent autophagy. The TRAIL sensitization capacity of CCB in TRAIL‑resistant HCC cells was abrogated by an ER stress inhibitor. In addition, we also revealed by flow cytometry and western blotting, respectively, that accelerated downregulation of TRAIL‑mediated c‑FLIP expression, DR5 activation and CD44 degradation/downregulation by NSAID resulted in activation of caspases and poly(ADP‑ribose) polymerase (PARP), leading to the sensitization of TRAIL‑resistant HCC cells to TRAIL and thereby reversal of TRAIL resistance. From these results, we propose that NSAID in combination with TRAIL may improve the antitumor activity of TRAIL in TRAIL‑resistant HCC, and this approach may serve as a novel strategy that maximizes the therapeutic efficacy of TRAIL for clinical application.
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http://dx.doi.org/10.3892/or.2020.7662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388578PMC
September 2020

Monosomal karyotype affecting outcomes of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission.

Eur J Haematol 2020 Sep 16;105(3):262-273. Epub 2020 Jun 16.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objectives: We evaluated the prognostic impact of MK on postremission outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) in the first complete remission (CR1).

Methods: We retrospectively analyzed 465 adult patients with AML who had received HSCT in the first CR between 2000 and 2016.

Results: In MK + AML, the median leukocyte count was significantly lower (P < .001) and no NPM1 mutation was found (P = .042). Multivariate analysis revealed that MK was the most powerful prognostic factors for OS (hazard ratio [HR], 2.6; P = .001), EFS (HR, 3.8; P < .001), and cumulative incidence of relapse (HR, 6.1; P < .001), compared to any other poor risk factors such as complex karyotype, FLT3-ITD mutations, old age, and higher leukocyte count. The adverse prognostic impact of MK tended to be more prominent in the younger age group (<40 years) (HR, 6.3, P < .001) than in the older age group (≥40 years) (HR, 3.4, P < .001).

Conclusion: Novel treatment modalities for MK + AML need to be investigated to reduce the risk of relapse after HSCT.
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http://dx.doi.org/10.1111/ejh.13434DOI Listing
September 2020

Balance performance and related soft tissue components across three age groups.

Health Care Women Int 2021 Jan 16;42(1):67-81. Epub 2019 Oct 16.

Graduate School of Public Health, San Diego State University, California, USA.

With the aging process, falls and related injuries are common and unwanted events among older women. Lost balance is the last step before the frequent experience of falls. After menopause, women's bone conditions regarding health and balance performance steeply decline often resulting in serious injury. Our purpose in the study is to identify balance performance and its associations with soft tissue components among Korean-American (KA) women with three menopausal conditions. Researchers conducted a cross-sectional study with 63 KA women divided into three age groups: 25-35 years (young), 45-55 years old (middle), and 65+ years (old). Lean and fat mass on the entire body, appendicular and gynoid areas were measured by using the dual X-ray absorptiometry. Static and dynamic balance and physical performance (floor sit to stand) were tested. We found that with increased aging, lean mass, fat and body mass index were changed; balance and physical performance decreased significantly. In regression models, age and fat ratio of android/gynoid changes explain static balance and physical performance; appendicular lean mass predicted dynamic balance. With advancing age, maintaining lean mass and proportion of fat accumulation is critical for stable balance.
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http://dx.doi.org/10.1080/07399332.2019.1678160DOI Listing
January 2021

Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells.

Mol Med Rep 2019 Oct 9;20(4):3301-3307. Epub 2019 Aug 9.

Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea.

c‑Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c‑Myc proto‑oncogene is a common event in the development and growth of various human types of cancer, the present study investigated whether oncogenic c‑Myc can alter natural killer (NK) cell‑mediated immunity through the expression of associated genes, using PCR, western blotting and flow cytometry assays. Furthermore, whether c‑Myc could influence the expression levels of natural killer group 2 member D (NKG2D) ligands, which are well known NK activation molecules, as well as NK cell‑mediated immunity, was investigated. c‑Myc was inhibited by 10058‑F4 treatment and small interfering RNA transfection. Upregulation of c‑Myc was achieved by transfection with a pCMV6‑myc vector. The inhibition of c‑Myc increased MHC class I polyeptide‑related sequence B and UL16 binding protein 1 expressions among NKG2D ligands, and the overexpression of c‑Myc suppressed the expression of all NKG2D ligands, except MHC class I polyeptide‑related sequence A. Furthermore, the alteration of c‑Myc activity altered the susceptibility of K562 cells to NK cells. These results suggested that the overexpression of c‑Myc may contribute to the immune escape of cancer cells and cell proliferation. Combined treatment with NK‑based cancer immunotherapy and inhibition of c‑Myc may achieve improved therapeutic results.
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http://dx.doi.org/10.3892/mmr.2019.10583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755160PMC
October 2019

Androgen therapy for patients with lower-risk myelodysplastic syndrome and significant cytopenia: a retrospective study.

Br J Haematol 2019 10 1;187(1):e4-e7. Epub 2019 Aug 1.

Department of Haematology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1111/bjh.16121DOI Listing
October 2019

Decitabine Versus Intensive Chemotherapy for Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia.

Clin Lymphoma Myeloma Leuk 2019 05 20;19(5):290-299.e3. Epub 2019 Feb 20.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Elderly patients with acute myeloid leukemia (AML) have generally had a poor prognosis with unfavorable clinical and biologic disease features. Hypomethylating agents have shown potential for treating medically unfit and elderly patients with AML.

Patients And Methods: We compared the outcomes of elderly patients with AML treated with decitabine and intensive chemotherapy (IC).

Results: The data from 107 patients with newly diagnosed AML aged ≥ 65 years were analyzed. The overall response rate was 38.6% and was significantly greater in the IC group than in the decitabine group (65.6% vs. 26.1%; P < .001). With a median follow-up duration of survivors of 14.8 months, the median overall survival (OS) and event-free survival were 12.3 months (95% confidence interval [CI], 10.0-14.7) and 2.0 months (95% CI, 2.0-2.0), respectively, which were not different between the 2 treatment groups. The FLT3-internal tandem duplication mutation (hazard ratio [HR], 2.637; 95% CI, 1.379-5.043; P = .003), complex karyotype (HR, 2.513; 95% CI, 1.258-5.020; P = .009), and peripheral blood blast percentage at diagnosis (HR, 1.983; 95% CI, 1.148-3.422; P = .014) were analyzed as independent prognostic factors for OS. A subgroup analysis for OS showed that IC was superior to decitabine for patients with the FLT3-internal tandem duplication mutation (P = .025) and poor risk cytogenetics, except for -7/del(7q) (P = .005), and decitabine was associated with longer OS for patients with -7/del(7q) (P = .077).

Conclusion: Decitabine showed a similar OS to IC, despite the lower response rate in patients. The clinical outcomes of specific subgroups seemed to differ with different treatment options. Optimal therapeutic approaches for elderly patients with AML should be further examined.
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http://dx.doi.org/10.1016/j.clml.2019.02.002DOI Listing
May 2019

Factors Influencing Falls in High- and Low-Risk Patients in a Tertiary Hospital in Korea.

J Patient Saf 2020 12;16(4):e376-e382

College of Nursing, Seoul National University, Seoul, Korea.

Objective: The purpose of this study was to explore the characteristics and predictors of falls in high- and low-risk inpatients in a tertiary hospital in Korea.

Methods: Fallers' data were extracted from quality improvement reports and electronic health records from June 1, 2014, to May 31, 2015. Data on nonfallers matched by the length of hospitalization and medical departments of fallers were extracted from electronic health records. Participants were classified into a high- or a low-risk group based on their Morse Fall Scale score, fall risk-related symptoms, and medications known to increase fall risk. Characteristics of falls and risk factors were analyzed using descriptive statistics and logistic regression analysis, respectively.

Results: In the high-risk group, education, surgery, department, impaired mobility, intravenous catheter placement, use of ambulatory aid, gait disturbance, and some medications were significantly different between the fallers and nonfallers. From these variables, education, operation, department, intravenous catheter placement, gait disturbance, and use of narcotics, vasodilators, antiarrhythmics, and hypnotics were statistically significant factors for falls. In the low-risk group, sex, age, length of hospitalization, surgery, department, diagnosis, and mental status were significantly different between the fallers and nonfallers. From these, sex, age, length of hospitalization, surgery, and liver-digestive diseases were statistically significant factors for falls.

Conclusions: Characteristics and risk factors for falls differed between the risk groups. Fall prevention strategies need to be tailored to the risk groups and fall risk assessment tools need to be revised accordingly.
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http://dx.doi.org/10.1097/PTS.0000000000000593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678652PMC
December 2020

Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome.

Blood Res 2018 Dec 17;53(4):288-293. Epub 2018 Dec 17.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT.

Methods: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis.

Results: The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival.

Conclusion: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.
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http://dx.doi.org/10.5045/br.2018.53.4.288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300680PMC
December 2018

Fludarabine/Melphalan 100 mg/m Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Biol Blood Marrow Transplant 2019 06 30;25(6):1116-1121. Epub 2018 Nov 30.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m/day on days -6 to -2 and melphalan at 100 mg/m on day -2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.032DOI Listing
June 2019

Physical activity, benefits, and barriers across the aging continuum.

Appl Nurs Res 2018 12 17;44:107-112. Epub 2018 Oct 17.

College of Nursing and Health Innovation, Arizona State University, United States of America. Electronic address:

Background: A growing body of evidence indicates the importance of physical activity during midlife period linked to the likelihood of healthy aging, while the likelihood of an individual engaging in physical activity depends largely on their perceived benefits and barriers to being physically active.

Aim: This study was to examine physical activity levels of midlife Korean American adults and their perceived benefits and barriers to physical activity compared with young and older adults.

Methods: We conducted a secondary analysis of data collected for a larger descriptive, cross-sectional study that was conducted with a sample of 517 Korean American adults in a Midwestern city. Data were collected using a survey questionnaire.

Results: A little more than half of the sample were women (57.1%), with a mean age of 41.6 (± 13.4). The study sample met the current guidelines for physical activity far less than the general U.S. population (30.4% -34.6 vs. 51.7%). Less midlife adults met the guidelines for moderate-intensity physical activity than older adults (34.2% vs. 57.4%), while less midlife adults met the guidelines for vigorous-intensity physical activity than young adults (24.8% vs. 40.6%). Midlife adults perceived fewer benefits than did young and older adults.

Conclusion: The findings indicate that midlife adults are less likely to engage in physical activity and probably more at risk for unhealthy ageing than young and older adults. Understanding benefits and barriers of target population is the first step in developing culturally and age-appropriate intervention to promote physical activity.
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http://dx.doi.org/10.1016/j.apnr.2018.10.003DOI Listing
December 2018

Blast Percentage of Bone Marrow Aspirate on Day 14 of Induction Chemotherapy Predicts Adult Acute Lymphoblastic Leukemia Treatment Outcomes.

Acta Haematol 2018;139(4):220-227. Epub 2018 Jun 1.

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.
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http://dx.doi.org/10.1159/000489025DOI Listing
March 2019

The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data.

Immune Netw 2018 Apr 22;18(2):e2. Epub 2018 Jan 22.

Department of Infectious Diseases, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D)/recipient-positive (R) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.
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http://dx.doi.org/10.4110/in.2018.18.e2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928417PMC
April 2018

Comparison of anthracyclines used for induction chemotherapy in patients with FLT3-ITD-mutated acute myeloid leukemia.

Leuk Res 2018 05 8;68:51-56. Epub 2018 Mar 8.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m/d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m/d × 3d; n = 51), or idarubicin (IDA; 12 mg/m/d × 3d; n = 33) in combination with cytarabine (100-200 mg/m/d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m/d) or IDA (8 or 12 mg/m/d) in addition to 5 days of cytarabine. Complete remission (CR) rates were 77.3%, 56.9%, and 69.7% for HD-DN, SD-DN, and IDA, respectively (P = 0.101; HD-DN vs. SD-DN, P = 0.036; HD-DN vs. IDA, P = 0.453; IDA vs. SD-DN, P = 0.237). The HD-DN showed higher overall survival (OS) and event-free survival (EFS) than SD-DN and IDA: the differences between HD-DN and SD-DN (P = 0.009 for OS and P = 0.010 for EFS) were statistically significant. Results of in vitro studies using FLT3-ITD-mutated cell lines supported these findings. In conclusion, HD-DN improved the CR rate, OS, and EFS of FLT3-ITD-mutated AML patients. HD-DN also tended to yield better outcomes than IDA, though the difference was not significant. The superiority of HD-DN over IDA should be confirmed in future studies.
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http://dx.doi.org/10.1016/j.leukres.2018.03.006DOI Listing
May 2018

The combination of ionizing radiation and proteasomal inhibition by bortezomib enhances the expression of NKG2D ligands in multiple myeloma cells.

J Radiat Res 2018 May;59(3):245-252

Department of Biochemistry, Pusan National University School of Medicine, Busandaehakro-49, Mulgeum-eup Yangsan-si Gyeongsangnam-do, 50612, South Korea.

Bortezomib, which is a potent proteasome inhibitor, has been used as a first-line drugs to treat multiple myeloma for a few decades, and radiotherapy has frequently been applied to manage acute bone lesions in the patients. Therefore, it was necessary to investigate what the benefits might be if the two therapies were applied simultaneously in the treatment of multiple myeloma. Since it was known that radiotherapy and proteasome inhibitors could increase the expression of NKG2D ligands through induction of protein synthesis and suppression of protein degradation of NKG2D ligands, respectively, we supposed that the combined treatment might further enhance the expression of NKG2D ligands. In this study, we analyzed the expression level of NKG2D ligands using multiplex PCR and flow cytometry after treatment of IM-9 and RPMI-8226 myeloma cells with bortezomib and ionizing radiation; we then assayed the susceptibility to NK-92 cells. Although the expression of only some kinds of NKG2D ligands were increased by treatment with bortezomib alone, five kinds of NKG2D ligands that we assayed were further induced at the surface protein level after combined treatment with ionizing radiation and bortezomib. Furthermore, combined treatment made myeloma cells more susceptible to NK-92 cells, compared with treatment with bortezomib alone. In conclusion, the combination therapy of ionizing radiation plus the proteasome inhibitor bortezomib is a promising therapeutical strategy for enhancing NK cell-mediated anticancer immune responses.
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http://dx.doi.org/10.1093/jrr/rry005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967576PMC
May 2018

Allogeneic hematopoietic cell transplantation for lymphoma: baseline and posttransplant prognostic factors.

Leuk Lymphoma 2018 08 22;59(8):1829-1839. Epub 2017 Nov 22.

a Department of Hematology , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea.

The present study aimed to investigate baseline and posttransplant prognostic factors for allogeneic hematopoietic cell transplantation (HCT) in 61 lymphoma patients. The 5-year probabilities of overall survival (OS), non-relapse mortality (NRM), progression-free survival (PFS), and event-free survival (EFS) were 31.1%, 28.8%, 38.8%, and 23.2%, respectively. Multivariate analysis demonstrated that the International Prognostic Index risk at HCT was a significantly independent prognostic factor for OS, NRM, PFS, and EFS, and chemosensitivity was a prognostic factor for OS, NRM, and EFS. The occurrence of chronic graft-versus-host disease (GVHD) was significantly associated with higher OS, but it was not with PFS or EFS. Various parameters of immune reconstitution at 1 month after transplantation were associated with clinical outcomes in different ways. Our study results might be helpful in selecting appropriate patients or adopting effective posttransplant treatment strategies, eventually leading to an improvement in outcomes after allogeneic HCT for lymphoma.
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http://dx.doi.org/10.1080/10428194.2017.1399310DOI Listing
August 2018

[Characteristics and Risk Factors for Falls in Tertiary Hospital Inpatients].

J Korean Acad Nurs 2017 Jun;47(3):420-430

College of Nursing, Seoul National University, Seoul, Korea.

Purpose: The aim of this study was to explore characteristics of and risk factors for accidental inpatient falls.

Methods: Participants were classified as fallers or non-fallers based on the fall history of inpatients in a tertiary hospital in Seoul between June 2014 and May 2015. Data on falls were obtained from the fall report forms and data on risk factors were obtained from the electronic nursing records. Characteristics of fallers and non-fallers were analyzed using descriptive statistics. Risk factors for falls were identified using univariate analyses and logistic regression analysis.

Results: Average length of stay prior to the fall was 21.52 days and average age of fallers was 61.37 years. Most falls occurred during the night shifts and in the bedroom and were due to sudden leg weakness during ambulation. It was found that gender, BMI, physical problems such elimination, gait, vision and hearing and medications such as sleeping pills, antiarrhythmics, vasodilators, and muscle relaxant were statistically significant factors affecting falls.

Conclusion: The findings show that there are significant risk factors such as BMI and history of surgery which are not part of fall assessment tools. There are also items on fall assessment tools which are not found to be significant such as mental status, emotional unstability, dizziness, and impairment of urination. Therefore, these various risk factors should be examined in the fall risk assessments and these risk factors should be considered in the development of fall assessment tools.
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http://dx.doi.org/10.4040/jkan.2017.47.3.420DOI Listing
June 2017

Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission.

Biol Blood Marrow Transplant 2017 Sep 25;23(9):1555-1566. Epub 2017 May 25.

Hematology-Oncology, Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.
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http://dx.doi.org/10.1016/j.bbmt.2017.05.025DOI Listing
September 2017

Diagnostic usefulness of dynamic changes of CMV-specific T-cell responses in predicting CMV infections in HCT recipients.

J Clin Virol 2017 02 30;87:5-11. Epub 2016 Nov 30.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: CMV-specific cell mediated immune responses before and after hematopoietic stem cell transplantation (HCT) can categorize patients as at high or low risk of CMV development.

Objectives: We evaluated the usefulness of the CMV-specific T-cell ELISPOT assay for predicting the development of CMV infections after HCT in recipients with donor-positive and recipient-positive CMV serology (D+/R+ ).

Study Design: CMV pp65 and IE1-specific ELISPOT assays were performed before HCT (D0), and at 30 (D30) and 90 (D90) days after HCT.

Results: Of the 84 HCT recipients with D+/R+, 42 (50%) developed≥1 episode of CMV infection. Thirty-nine (64%) of 61 patients with Δ(D30-D0) pp65<42 developed CMV infections compared with 3 (14%) of 21 patients with Δ(D30-D0) pp65≥42 (P<0.001). Twenty-three (74%) of 31 patients with Δ(D30-D0) IE1<-4 developed CMV infections compared with 19 (37%) of 51 patients with Δ(D30-D0) IE1≥-4 (P=0.001). pp65 Δ(D30-D0) ≥42 had 93% sensitivity for ruling out subsequent CMV infection, and pp65 Δ(D30-D0)<42 followed by Δ(D30-D0) IE1<-4 had 100% specificity for ruling in the subsequent CMV infection. In addition, 10 (53%) of 19 patients with Δ(D90-D30) pp65<23 had relapsing CMV infections, compared with 3 (15%) of 20 patients with Δ(D90-D30) pp65≥23 (P=0.02). The sensitivity and specificity of Δ(D90-D30) pp65 were 77% (95% CI 50-92) and 65% (95% CI, 46-81).

Conclusion: Dynamic change in the CMV-specific ELISPOT assay before versus after HCT appears to predict the subsequent development of CMV infection and relapsing CMV infection.
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http://dx.doi.org/10.1016/j.jcv.2016.11.012DOI Listing
February 2017

Acupuncture does not protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in a preclinical mouse model of Parkinson's disease.

Neuroreport 2017 Jan;28(1):50-55

aDepartment of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan bDepartment of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine cDepartment of Neurology and Neuroscience Research Institute, Seoul National University Hospital, Seoul National University College of Medicine dCancer Research Institute, Seoul National University Hospital, Seoul eDepartment of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang fDepartment of Neurology, Myongji Hospital, Seonam University College of Medicine, Goyang, Korea gSecond Department of Neurology, The China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, PR China.

Acupuncture treatment, a complementary and alternative medicine, is associated with a suggested neuroprotective effect in previous preclinical studies of Parkinson's disease (PD); however, results from human clinical trials have been mixed or unsuccessful. Recent systematic reviews of translational neuroprotective studies showed that the supposed efficacy is confounded by low methodological quality, particularly by a lack of randomization and concealed allocation. We sought to replicate previous experimental findings with a study design that mitigates the introduction of bias, including randomization, blinded outcome measures, sham acupuncture application, and allocation concealment by blinded neurotoxin administration. We performed 12 sessions of manual acupuncture at acupoint GB34 (yanglingquan) in mice that were administered the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin for five consecutive days. In this animal model of PD, acupuncture treatment did not attenuate tyrosine hydroxylase-immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced striatal tyrosine hydroxylase expression. Our results indicate that acupuncture is not neuroprotective against nigrostriatal loss in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD.
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http://dx.doi.org/10.1097/WNR.0000000000000709DOI Listing
January 2017

The Diagnostic Accuracy of the Berg Balance Scale in Predicting Falls.

West J Nurs Res 2017 11 26;39(11):1502-1525. Epub 2016 Oct 26.

2 San Diego State University, San Diego, CA, USA.

This study aimed to evaluate the predictive validity of the Berg Balance Scale (BBS) as a screening tool for fall risks among those with varied levels of balance. A total of 21 studies reporting predictive validity of the BBS of fall risk were meta-analyzed. With regard to the overall predictive validity of the BBS, the pooled sensitivity and specificity were 0.72 and 0.73, respectively; the accuracy curve area was 0.84. The findings showed statistical heterogeneity among studies. Among the sub-groups, the age group of those younger than 65 years, those with neuromuscular disease, those with 2+ falls, and those with a cutoff point of 45 to 49 showed better sensitivity with statistically less heterogeneity. The empirical evidence indicates that the BBS is a suitable tool to screen for the risk of falls and shows good predictability when used with the appropriate criteria and applied to those with neuromuscular disease.
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http://dx.doi.org/10.1177/0193945916670894DOI Listing
November 2017

Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia.

Biol Blood Marrow Transplant 2016 11 12;22(11):2065-2076. Epub 2016 Aug 12.

Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. Electronic address:

The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 10/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).
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http://dx.doi.org/10.1016/j.bbmt.2016.08.008DOI Listing
November 2016

Non-myeloablative conditioning for lower-risk myelodysplastic syndrome with bone marrow blasts less than 5 %-a feasibility study.

Ann Hematol 2016 Jun 22;95(7):1151-61. Epub 2016 Apr 22.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Reduced-intensity conditioning (RIC) regimens can cause decreased non-relapse mortality (NRM) but lead to higher relapse rates in higher-risk myelodysplastic syndrome (MDS). However, relapse is not the main problem after hematopoietic cell transplantation (HCT) in lower-risk MDS, and post-transplant outcomes may therefore improve with less intense non-myeloablative conditioning (NMC) regimens. We here report the results of a single-center feasibility study of NMC with cyclophosphamide-fludarabine-antithymocyte globulin (CyFluATG) in MDS patients with bone marrow blasts <5 %. We compared post-transplant outcomes between CyFluATG and a RIC regimen, busulfan-fludarabine-antithymocyte globulin (BuFluATG). Fifteen MDS patients received allogeneic HCT after CyFluATG conditioning comprising cyclophosphamide (100 mg/kg), fludarabine (150 mg/m(2)), and ATG, and 30 MDS historical control patients received BuFluATG conditioning which contained busulfan (8 [oral] or 6.4 [i.v.] mg/kg), fludarabine, and ATG. The 4-year overall survival (OS) and NRM rates were 80.0 and 20.0 % for CyFluATG and 73.3 and 20.0 % for BuFluATG, respectively. Neutrophil and platelet engraftment was significantly faster with CyFluATG than BuFluATG (median 12 vs. 14 days, P = 0.005 for neutrophils; median 15 vs. 21 days, P = 0.032 for platelets). CyFluATG produced a faster immune reconstitution of T-cells at 1 month after HCT than BuFluATG. Fertility was maintained after HCT with CyFluATG. In conclusion, the CyFluATG regimen is feasible in lower-risk MDS patients in terms of adequate engraftment and low NRM.
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http://dx.doi.org/10.1007/s00277-016-2679-xDOI Listing
June 2016

Complete reduction of highly concentrated contaminants in piggery waste by a novel process scheme with an algal-bacterial symbiotic photobioreactor.

J Environ Manage 2016 Jul 18;177:202-12. Epub 2016 Apr 18.

Department of Biosciences & Environmental Engineering, The Catholic University of Korea, San 43-1 Yeokgok-dong, Wonmi-ku, Bucheon, Kyunggi-do, Republic of Korea. Electronic address:

The complete reduction of highly concentrated contaminants in piggery waste was achieved with an innovative process scheme consecutively combining autothermal thermophilic aerobic digestion (ATAD), an expanded granular sludge bed (EGSB) and a microalgal-bacterial symbiotic vertical photobioreactor (VPBR), followed by biomass recycling for effluent polishing. Contaminants in piggery waste, such as high organic and inorganic matter, total nitrogen (TN), and total phosphorus (TP) contents, were successfully reduced in the newly implemented system. The concentrations of volatile solids (VS) and the chemical oxygen demand (COD) for organic matter in the feed were reduced by approximately 99.3% and 99.7%, respectively, in the innovative system. The overall reduction efficiencies in TN, ammoniacal nitrogen, and TP were 98.8, 98.4, and 93.5%, respectively, through ammonia gas emission, coagulated sludge disposal, and the algal-bacterial symbiotic polishing process. Fecal coliform density was decreased to <1.7 × 10(4) CFU g(-1) total solids. Biogas and CH4 in the EGSB were generated in the range of 0.36-0.79 and 0.18-0.44 L g(-1) [VS removed], respectively, and contained 245 ± 19 ppm (v/v) [H2S].
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http://dx.doi.org/10.1016/j.jenvman.2016.04.025DOI Listing
July 2016