Publications by authors named "Inho Kim"

222 Publications

Identification of an Optimal Population for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Mature T and NK Cell Neoplasms.

In Vivo 2021 Jul-Aug;35(4):2379-2390

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea;

Background/aim: The prognosis of mature T and natural killer (NK) cell neoplasms still remains dismal, despite the advancements in the understanding of the heterogeneous features of these diseases. As allogeneic stem cell transplantation (alloSCT) is an attractive salvage option for relapsed/refractory patients, we conducted this study to identify those who might benefit the most from alloSCT.

Patients And Methods: This was a retrospective, single-center, longitudinal cohort study of patients who received alloSCT between December 2019 and January 2000.

Results: The median relapse-free survival and overall survival were 4.4 and 10.0 months, respectively. Disease control status at alloSCT and number of previous treatments were associated with survival outcomes. The conditioning intensity did not significantly alter survival.

Conclusion: AlloSCT offers a cure chance for selected relapsed or refractory T and NK cell neoplasms, especially when used early and the disease is well controlled prior to transplantation.
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http://dx.doi.org/10.21873/invivo.12515DOI Listing
June 2021

Design of mid-infrared filter array based on plasmonic metal nanodiscs array and its application to on-chip spectrometer.

Sci Rep 2021 Jun 9;11(1):12218. Epub 2021 Jun 9.

Center for Neuromorphic Engineering, Korea Institute of Science and Technology, Seoul, 02792, Korea.

Mid-infrared wavelengths are called the molecular fingerprint region because it contains the fundamental vibrational modes inherent to the substances of interest. Since the mid-infrared spectrum can provide non-destructive identification and quantitative analysis of unknown substances, miniaturized mid-infrared spectrometers for on-site diagnosis have attained great concern. Filter-array based on-chip spectrometer has been regarded as a promising alternative. In this study, we explore a way of applying a pillar-type plasmonic nanodiscs array, which is advantageous not only for excellent tunability of resonance wavelength but also for 2-dimensional integration through a single layer process, to the multispectral filter array for the on-chip spectrometer. We theoretically and experimentally investigated the optical properties of multi-periodic triangular lattices of metal nanodiscs array that act as stopband filters in the mid-infrared region. Soft-mold reverse nanoimprint lithography with a subsequent lift-off process was employed to fabricate the multispectral filter array and its filter function was successfully extracted using a Fourier transform infrared microscope. With the measured filter function, we tested the feasibility of target spectrum reconstruction using a Tikhonov regularization method for an ill-posed linear problem and evaluated its applicability to the infrared spectroscopic sensor that monitors an oil condition. These results not only verify that the multispectral filter array composed of stopband filters based on the metal nanodiscs array when combined with the spectrum reconstruction technique, has great potential for use to a miniaturized mid-infrared on-chip spectrometer, but also provide effective guidance for the filter design.
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http://dx.doi.org/10.1038/s41598-021-91762-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190067PMC
June 2021

Busulfan plus melphalan melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma.

Ther Adv Hematol 2021 7;12:20406207211012985. Epub 2021 May 7.

Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul 03080, Republic of Korea.

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented.

Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019.

Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates.

Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient's response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.
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http://dx.doi.org/10.1177/20406207211012985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111524PMC
May 2021

Should patients receive consolidation chemotherapy before reduced intensity allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission?

Ther Adv Hematol 2021 20;12:20406207211001135. Epub 2021 Apr 20.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam 463-707, Republic of Korea.

Background: For acute myeloid leukemia (AML) patients, the role of bridging consolidation chemotherapy after achieving first complete remission (CR1) in the transplant setting is a frequently debated issue. The lack of data from Asian patients led us to conduct this study.

Methods: We retrospectively studied outcomes of 106 patients in CR1 undergoing allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) based on their exposure to pre-transplant consolidation chemotherapy. There were 35 in the no consolidation group 71 in the consolidation group.

Results: The median relapse free survival (RFS) was 9 months for the no consolidation group and 51 months for consolidation group ( = 0.023). The median overall survival was 32 months for the no consolidation group and not reached for the consolidation group ( = 0.034). Multivariate analysis recognized consolidation and poor cytogenetics as adverse prognostic factors for RFS. Moreover, RFS was better in patients with a shorter time lapse between last chemotherapy and alloSCT in both the no consolidation group and the consolidation group. Consolidation chemotherapy did not negatively affect neutrophil and platelet engraftment, infection rates, or acute graft--host disease (GVHD) incidence. On the other hand, patients undergoing consolidation chemotherapy showed trends towards a more severe degree of chronic GVHD.

Conclusion: The exposure to consolidation chemotherapy in CR1 prior to alloSCT with RIC conditioning did not negatively impact the outcomes in Korean AML patients, for whom a suitable donor is rarely immediately available. Therefore, post-remission consolidation chemotherapy is a reasonable option if required.
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http://dx.doi.org/10.1177/20406207211001135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060779PMC
April 2021

Spiking Neural Network (SNN) With Memristor Synapses Having Non-linear Weight Update.

Front Comput Neurosci 2021 11;15:646125. Epub 2021 Mar 11.

Center for Neuromorphic Engineering, Korea Institutes of Science and Technology, Seoul, South Korea.

Among many artificial neural networks, the research on Spike Neural Network (SNN), which mimics the energy-efficient signal system in the brain, is drawing much attention. Memristor is a promising candidate as a synaptic component for hardware implementation of SNN, but several non-ideal device properties are making it challengeable. In this work, we conducted an SNN simulation by adding a device model with a non-linear weight update to test the impact on SNN performance. We found that SNN has a strong tolerance for the device non-linearity and the network can keep the accuracy high if a device meets one of the two conditions: 1. symmetric LTP and LTD curves and 2. positive non-linearity factors for both LTP and LTD. The reason was analyzed in terms of the balance between network parameters as well as the variability of weight. The results are considered to be a piece of useful prior information for the future implementation of emerging device-based neuromorphic hardware.
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http://dx.doi.org/10.3389/fncom.2021.646125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996210PMC
March 2021

Pegteograstim prophylaxis for chemotherapy-induced neutropenia and febrile neutropenia: a prospective, observational, postmarketing surveillance study in Korea.

Support Care Cancer 2021 Sep 8;29(9):5383-5390. Epub 2021 Mar 8.

Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunwhandoro, Dong-gu, Ulsan, 44033, Republic of Korea.

Purpose: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies.

Methods: This study was conducted at 18 sites in Korea between November 2015 and August 2018.

Results: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18-88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified.

Conclusion: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases.
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http://dx.doi.org/10.1007/s00520-021-06127-7DOI Listing
September 2021

Updated recommendations for the treatment of venous thromboembolism.

Blood Res 2021 Mar;56(1):6-16

Division of Hematology-Oncology, Department of Internal Medicine, CHA University School of Medicine, Seongnam, Korea.

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.
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http://dx.doi.org/10.5045/br.2021.2020083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987480PMC
March 2021

Immunogenicity and safety of a live herpes zoster vaccine in hematopoietic stem cell transplant recipients.

BMC Infect Dis 2021 Jan 26;21(1):117. Epub 2021 Jan 26.

Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination.

Methods: Live HZ vaccine was administered to patients 2-5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored.

Results: Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2-5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96-5.07] vs 5.05, 95% CI [2.50-10.20] vs 2.97, 95% CI [2.30-3.83] vs 1.42, 95% CI [1.08-1.86]). The GMFR of cellular immune responses was highest in the HSCT 2-5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period.

Conclusion: Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.
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http://dx.doi.org/10.1186/s12879-021-05806-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836155PMC
January 2021

A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Intermediated-risk Acute Myeloid Leukemia Patients.

In Vivo 2021 Jan-Feb;35(1):617-622

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea;

Background/aim: For intermediate risk acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation (alloSCT) and chemotherapy are equally recommended as consolidation after first complete remission (CR1). In real-world, alloSCT might not be readily available, but there is paucity of data on the optimal timing of alloSCT for these patients.

Patients And Methods: In this pilot study, we compared the outcomes of 13 patients undergoing alloSCT in CR1 with 13 patients undergoing alloSCT after relapse (non-CR1) to examine whether upfront alloSCT yields a better prognosis.

Results: There were no differences between the two groups with regards to relapse-free survival (p=0.507) and overall survival (p=0.798). There were more chronic graft-versus-host-disease (GVHD) in the CR1 group compared to the non-CR group (p=0.001), but no difference in acute GVHD.

Conclusion: The outcome of alloSCT after relapse is not inferior to that of alloSCT in CR1, supporting the role of alloSCT after relapse in the setting of limited donors and resources.
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http://dx.doi.org/10.21873/invivo.12299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880739PMC
June 2021

A 2D material-based floating gate device with linear synaptic weight update.

Nanoscale 2020 Dec;12(48):24503-24509

Center for Neuromorphic Engineering, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea.

Neuromorphic computing is of great interest among researchers interested in overcoming the von Neumann computing bottleneck. A synaptic device, one of the key components to realize a neuromorphic system, has a weight that indicates the strength of the connection between two neurons, and updating this weight must have linear and symmetric characteristics. Especially, a transistor-type device has a gate terminal, separating the processes of reading and updating the conductivity, used as a synaptic weight to prevent sneak path current issues during synaptic operations. In this study, we fabricate a top-gated flash memory device based on two-dimensional (2D) materials, MoS2 and graphene, as a channel and a floating gate, respectively, and Al2O3 and HfO2 to increase the tunneling efficiency. We demonstrate the linear weight updates and repeatable characteristics of applying negative/positive pulses, and also emulate spike timing-dependent plasticity (STDP), one of the learning rules in a spiking neural network (SNN).
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http://dx.doi.org/10.1039/d0nr07403aDOI Listing
December 2020

Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial.

Lancet Oncol 2020 12 29;21(12):1630-1642. Epub 2020 Oct 29.

Department of Hematology, University Hospital, Nantes, France.

Background: Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma.

Methods: In this randomised, double-blind, multicentre, phase 3 trial, patients aged 18 years or older with relapsed or refractory multiple myeloma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received one to three previous therapies were enrolled from 90 hospitals in 16 countries. Eligible patients were randomly assigned (2:1) centrally using an interactive response technology system and a block size of three to receive venetoclax (800 mg per day orally) or placebo with bortezomib (1·3 mg/m subcutaneously or intravenously and dexamethasone (20 mg orally). Treatment was given in 21-day cycles for the first eight cycles and 35-day cycles from the ninth cycle until disease progression, unacceptable toxicity, or patient withdrawal. Randomisation was stratified by previous exposure to a proteasome inhibitor and the number of previous therapies. Sponsors, investigators, study site personnel, and patients were masked to the treatment allocation throughout the study. The primary endpoint was independent review committee-assessed progression-free survival in the intention-to-treat population. Safety analyses were done in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02755597.

Findings: Between July 19, 2016, and Oct 31, 2017, 291 patients were randomly assigned to receive venetoclax (n=194) or placebo (n=97). With a median follow-up of 18·7 months (IQR 16·6-21·0), median progression-free survival according to independent review committee was 22·4 months (95% CI 15·3-not estimable) with venetoclax versus 11·5 months (9·6-15·0) with placebo (hazard ratio [HR] 0·63 [95% CI 0·44-0·90]; p=0·010). The most common grade 3 or worse treatment-emergent adverse events were neutropenia (35 [18%] of 193 patients in the venetoclax group vs seven [7%] of 96 patients in the placebo group), pneumonia (30 [16%] vs nine [9%]), thrombocytopenia (28 [15%] vs 29 [30%]), anaemia (28 [15%] vs 14 [15%]), and diarrhoea (28 [15%] vs 11 [11%]). Serious treatment-emergent adverse events occurred in 93 (48%) patients in the venetoclax group and 48 (50%) patients in the placebo group, with eight (4%) treatment-emergent fatal infections reported in the venetoclax group and none reported in the placebo group. Three deaths in the venetoclax group (two from pneumonia and one from septic shock) were considered treatment-related; no deaths in the placebo group were treatment-related.

Interpretation: The primary endpoint was met with a significant improvement in independent review committee-assessed progression-free survival with venetoclax versus placebo plus bortezomib and dexamethasone. However, increased mortality was seen in the venetoclax group, mostly because of an increased rate of infections, highlighting the importance of appropriate selection of patients for this treatment option.

Funding: AbbVie and Genentech.
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http://dx.doi.org/10.1016/S1470-2045(20)30525-8DOI Listing
December 2020

Author Correction: Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia.

Sci Rep 2020 Oct 20;10(1):18198. Epub 2020 Oct 20.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-74316-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576199PMC
October 2020

High Cell-Free DNA Levels in Cerebrospinal Fluid Predict Leptomeningeal Seeding of Hematologic Malignancy.

J Clin Neurol 2020 Oct;16(4):581-585

Division of Hematology/Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background And Purpose: The main difficulty when diagnosing leptomeningeal metastases (LMSs) is the low sensitivity of cytology. Cancer cells release cell-free DNA (cfDNA) during proliferation and apoptosis, and so we analyzed the cfDNA level as a biomarker for LMSs in hematologic malignancy.

Methods: This study prospectively enrolled 20 patients with hematologic malignancy who underwent cerebrospinal fluid (CSF) analysis. LMS was diagnosed based on both CSF cytology and clinical findings.

Results: The CSF level of cfDNA was higher in patients with LMSs (108.17±84.84 ng/mL, mean±standard deviation) than in non-LMS patients (14.23±2.78 ng/mL). The sensitivity of cfDNA was higher than that of cytology (100% vs. 87%).

Conclusions: The cfDNA level in the CSF can be used as a supplemental marker for diagnosing LMS in hematologic malignancy patients.
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http://dx.doi.org/10.3988/jcn.2020.16.4.581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541998PMC
October 2020

Leukemic stem cell phenotype is associated with mutational profile in acute myeloid leukemia.

Korean J Intern Med 2021 03 20;36(2):401-412. Epub 2020 Aug 20.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

Background/aims: Understanding leukemic stem cell (LSC) is important for acute myeloid leukemia (AML) treatment. However, association of LSC with patient prognosis and genetic information in AML patients is unclear.

Methods: Here we investigated the associations between genetic information and the various LSC phenotypes, namely multipotent progenitor (MPP)-like, lymphoid primed multipotent progenitor (LMPP)-like and granulocyte-macrophage progenitors (GMP)-like LSC in 52 AML patients.

Results: In secondary AML patients, MPP-like LSC was significantly higher than de novo AML (p = 0.0037). The proportion of MPP-like LSC was especially high in post-myeloproliferative neoplasm AML (p = 0.0485). There was no correlation between age and LSC phenotype. Mutations of KRAS and NRAS were observed in MPP-like LSC dominant patients, TP53 and ASXL1 mutations in LMPP-like LSC dominant patients, and CEBPA, DNMT3A and IDH1 mutations in GMP-like LSC dominant patients. Furthermore, KRAS mutation was significantly associated with MPP-like LSC expression (p = 0.0540), and TP53 mutation with LMPP-like LSC expression (p = 0.0276). When the patients were separated according to the combined risk including next generation sequencing data, the poorer the prognosis, the higher the LMPP-like LSC expression (p = 0.0052). This suggests that the dominant phenotype of LSC is one of the important factors in predicting the prognosis and treatment of AML.

Conclusion: LSC phenotype in AML is closely associated with the recurrent mutations which has prognostic implication. Further research to confirm the meaning of LSC phenotype in the context of genetic aberration is warranted.
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http://dx.doi.org/10.3904/kjim.2020.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969060PMC
March 2021

Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant? (Running Title: The Role of Salvage alloSCT in MM).

J Clin Med 2020 Jul 23;9(8). Epub 2020 Jul 23.

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

Background: Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear.

Methods: Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017.

Results: The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%).

Conclusion: AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.
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http://dx.doi.org/10.3390/jcm9082354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466005PMC
July 2020

Reversible switching mode change in TaO-based resistive switching memory (ReRAM).

Sci Rep 2020 Jul 9;10(1):11247. Epub 2020 Jul 9.

Electronic Materials Research Center, Korea Institute of Science and Technology, Seoul, South Korea.

We report the complementary resistive switching (CRS) behaviors in a tantalum-oxide based resistive switching memory device that reversibly changes its switching mode between bipolar switching (BRS) and CRS in a single memory cell depending on the operation (compliance current) and fabrication (oxygen scavenger layer thickness) conditions. In addition, the origin of the switching mode transition was investigated through electrical and optical measurement, where the conductance is believed to be determined by two factors: formation of conductive filament and modulation of Schottky barrier. This result helps design a resistive switching device with desirable and stable switching behavior.
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http://dx.doi.org/10.1038/s41598-020-68211-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347604PMC
July 2020

MED-TMA: A clinical decision support tool for differential diagnosis of TMA with enhanced accuracy using an ensemble method.

Thromb Res 2020 09 27;193:154-159. Epub 2020 Jun 27.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Center for Precision Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Considering difficulties in on-site ADAMTS13 testing and the performance instability of PLASMIC score according to ethnicity, we developed a prediction tool, MED-TMA (machine learning (ML) method for differential diagnosis (DDx) of thrombotic microangiopathy (TMA)) to support clinical decision. Data from 319 patients visiting 31 hospitals in Korea clinically diagnosed with primary TMA was randomly separated by 2:1 into two groups - the development dataset (D-set, n = 212), the validation dataset (V-set, n = 107). Feature elimination was conducted to select optimal clinical predictors. We developed the model with the selected features using ML methods, verifying using V-set. After the feature elimination using 19 clinical variables, five variables were selected with high importance value. Among nine ML methods, four ML methods were chosen considering the Area Under the Curves (AUC) and the correlation between the methods using D-set. We developed MED-TMA based on an optimized ensemble model with the selected four ML methods resulting in AUC values of 0.945 and 0.924 in D-set and V-set, respectively. In addition to the binary outcome, MED-TMA was capable of providing a probability for DDx of TMA. The ensemble approach driven MED-TMA showed comparable accurate and intuitive decision support for DDx of TMA to that of the existing models based on a single ML method. We provide a web-based nomogram for the appropriate use of effective but costly therapeutics to treat TMA patients (http://hematology.snu.ac.kr/medtma/).
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http://dx.doi.org/10.1016/j.thromres.2020.06.045DOI Listing
September 2020

Preconditioning Absolute Lymphocyte Count and Transplantation Outcomes in Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Reduced-Intensity Conditioning and Antithymocyte Globulin Treatment.

Biol Blood Marrow Transplant 2020 10 17;26(10):1855-1860. Epub 2020 Jun 17.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

The integration of antithymocyte globulin (ATG) into therapy has significantly reduced the incidence of graft-versus-host disease (GVHD) and is being actively used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The ATG dosage is determined by the recipient's body weight, but some insist that this approach does not reflect the actual target of ATG. In this respect, weight-based dosing may lead to ATG overdose, particularly in recipients with a relatively low absolute lymphocyte count (ALC). We retrospectively analyzed 84 patients with acute leukemia or myelodysplastic syndrome who underwent matched related donor (MRD) allo-HSCT with reduced-intensity conditioning (RIC) at a single institution. Patients were dichotomized according to the ALC measured on the first day of conditioning (day -7) to investigate the associations of the ALC with GVHD and survival outcomes. The median duration of follow-up was 29 months. The preconditioning ALC was closely correlated with the ALC at the first ATG administration (day -3). The cumulative incidences of both acute GVHD and chronic GVHD were significantly lower in the preconditioning ALC <500/μL group compared with the ALC ≥500/μL group. There was no significant difference in disease relapse incidence between the 2 groups; however, mortality was significantly higher in the ALC <500/μL group. Multivariate analysis including disease status, modified European Blood and Marrow Transplantation score, and preconditioning ALC (≥500/μL versus <500/μL) identified disease status and ALC as being independently associated with overall survival (OS). In particular, infection was the most common cause of death in the ALC <500/μL group. Our data suggest that uniform weight-based ATG dosing in MRD allo-HSCT with RIC is associated with an increase in nonrelapse mortality and a relatively inferior OS in patients with a significantly low preconditioning ALC. Therefore, alternative strategies for the integration of ATG should be considered in allo-HSCT, at least for patients with a substantially low preconditioning ALC.
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http://dx.doi.org/10.1016/j.bbmt.2020.06.005DOI Listing
October 2020

Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia.

Sci Rep 2020 06 10;10(1):9370. Epub 2020 Jun 10.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Helicobacter pylori (H. pylori) infection is on the rise as a cause of immune thrombocytopenia (ITP). It has been suggested that platelet recovery can be achieved following successful microbial eradication, although, the exact pathophysiology has yet to be fully elucidated. This study evaluated the long-term effects of H. pylori eradication monotherapy on platelet count recovery in patients with ITP. H. pylori eradication was analysed in 61 ITP patients. Patients who maintained a complete response (CR) for more than six months were classified as sustained responders (SR). The prevalence of H. pylori infection was 54.3% (75/138), and the success rate of eradication with first-line therapy was 71.4% (35/49). Patients who had achieved a CR at 2 months maintained a higher platelet count thereafter. At 1 year following eradication, platelet counts had increased 2.78 times in the eradicated group, 1.36 times in the sustained infection group, and 1.33 times in the no infection group compared with the baseline (P = 0.016).
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http://dx.doi.org/10.1038/s41598-020-66460-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287131PMC
June 2020

Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia.

BMC Infect Dis 2020 Jun 9;20(1):404. Epub 2020 Jun 9.

Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro 101, Jongro-gu, Seoul, 03080, Republic of Korea.

Background: Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy.

Methods: We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital.

Results: Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3-284.1; P < 0.001); isolation of carbapenem-resistant Acinetobacter baumannii (aOR: 19.4, 95%CI: 3.4-112.5; P = 0.001) in the prior year; and days from chemotherapy to GNB bacteremia (aOR: 1.1 per day, 95%CI: 1.1-1.2; P < 0.001). Carba-NS bacteremia was independently associated with in-hospital mortality (aOR: 6.6, 95%CI: 3.0-14.8; P < 0.001).

Conslusion: Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.
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http://dx.doi.org/10.1186/s12879-020-05131-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282079PMC
June 2020

BLESeis: Low-Cost IoT Sensor for Smart Earthquake Detection and Notification.

Sensors (Basel) 2020 May 23;20(10). Epub 2020 May 23.

Department of Civil and Environmental Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.

The Internet of Things (IoT) has been implemented to provide solutions for certain event detection because of ease of installation, computing and communication capability, and cost-effectiveness. Seismic event detection, however, is still a challenge due to a lack of high-fidelity sensing and classification efficiency. This study proposes BLESeis, an IoT sensor for smart earthquake detection. BLESeis comprises three main parts: (1) high-fidelity vibration sensing using a MEMS accelerometer and digital filtering; (2) an embedded earthquake detection algorithm; (3) BLE (Bluetooth low energy) beacon for earthquake notification. For high-fidelity vibration sensing, a triggering algorithm and embedded finite impulse response (FIR) low-pass filter are developed. The acquired vibration is then classified by the earthquake detection algorithm developed to identify the earthquake signal from other vibration sources using time and frequency domain analysis. Upon detection of an earthquake, the BLE beacon broadcasts using the proposed data packet for efficient notification and visualization. The performance of the proposed system is evaluated through numerical simulations and a set of experiments using shaking table tests. The experiments show the feasibility of the low-cost earthquake detection and notification system.
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http://dx.doi.org/10.3390/s20102963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294427PMC
May 2020

Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina.

J Clin Med 2020 May 2;9(5). Epub 2020 May 2.

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

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR's diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.
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http://dx.doi.org/10.3390/jcm9051313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290712PMC
May 2020

Characterization and Prognosis of Secondary Acute Myeloid Leukemia in an Asian Population: AML With Antecedent Hematological Disease Confers Worst Outcomes, Irrespective of Cytogenetic Risk.

Anticancer Res 2020 May;40(5):2917-2924

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea

Background/aim: Acute myeloid leukemia (AML) is a biologically heterogeneous disease that can be classified into de novo AML and secondary AML. Secondary AML can be further divided into therapy-related AML (t-AML) or AML evolving from antecedent hematological disorder (AHD-AML). This study evaluated the characteristics and prognosis of secondary AML in a homogeneous East Asian population who are often under-represented.

Patients And Methods: This was a retrospective, longitudinal cohort study of Korean AML patients over 18 years old treated between January 2000 and December 2013. A total of 437 de novo AML (80.3%), 41 t-AML (7.5%), and 66 AHD-AML (12.1%) were evaluated.

Results: First, we found that secondary AML constituted about 19.7% of all AML cases, and t-AML was more prevalent than AHD-AML. Second, we determined AHD-AML as a prognostic factor for inferior survival, independent of other risk factors (HR=2.137, 95%CI=1.534-2.977, p<0.001). The induction response rates correlated well with the overall survival. Furthermore, AHD-AML was associated with worst treatment outcomes and prognosis regardless of cytogenetic risk or age. Interestingly, t-AML was generally associated with better outcomes compared to AHD-AML despite the similarities in treatment schema.

Conclusion: Secondary AML represents a broad spectrum of diseases and t-AML should be addressed separately from AHD-AML.
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http://dx.doi.org/10.21873/anticanres.14269DOI Listing
May 2020

Association of HSV-1 and Reduced Oral Bacteriota Diversity with Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

J Clin Med 2020 Apr 11;9(4). Epub 2020 Apr 11.

Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Seoul 03080, Korea.

Oral mucositis (OM) is a common complication of chemotherapy and remains a significant unmet need. The aim of this study was to investigate the role of oral bacteriota and HSV-1 in OM. Forty-six patients admitted for autologous hematopoietic stem cell transplantation were longitudinally evaluated for OM, Candida, HSV-1, and leukocyte count, and buccal mucosal bacterial samples were obtained during their admission period. The bacterial communities collected at the baseline and post-chemotherapy, chosen from the time with the highest severity, were analyzed by sequencing the 16S rRNA gene. Twenty (43.5%) patients developed OM, the severity of which ranged from 1 to 5 according to the Oral Mucositis Assessment Scale (OMAS). Chemotherapy significantly increased the prevalence of HSV-1 detection but not that of Candida. The bacterial communities of patients after conditioning chemotherapy were characterized by aberrant enrichment of minor species and decreased evenness and Shannon diversity. After adjustment for age, gender, and neutropenia, the presence of HSV-1 was associated with the incidence of OM (odds ratio = 3.668, = 0.004), while the decrease in Shannon diversity was associated with the severity of OM ( = 0.533 ± 0.220, = 0.015). The control of HSV-1 and restoration of oral bacterial diversity may be a novel option to treat or prevent OM.
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http://dx.doi.org/10.3390/jcm9041090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230275PMC
April 2020

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study.

Korean J Intern Med 2021 01 14;36(1):194-204. Epub 2020 Apr 14.

Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Korea.

Background/aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL.

Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012.

Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively).

Conclusion: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
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http://dx.doi.org/10.3904/kjim.2019.210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820637PMC
January 2021

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome.

Blood Res 2020 Mar 30;55(1):27-34. Epub 2020 Mar 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.

Methods: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.

Results: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (=0.844), and 55%, 45%, and 45% for the OS rate (=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.

Conclusion: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.
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http://dx.doi.org/10.5045/br.2020.55.1.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106115PMC
March 2020

KCDC Risk Assessments on the Initial Phase of the COVID-19 Outbreak in Korea.

Osong Public Health Res Perspect 2020 Apr;11(2):67-73

Division of Risk Assessment and International Cooperation, Korea Centers for Disease Control and Prevention, Cheongju, Korea.

Objectives: This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the Korea Centers for Disease Control and Prevention (KCDC), from the point of detection to the provision of basic information to the relevant public health authorities.

Methods: To estimate the overall risk of specific public health events, probability, and impact at the country-level were evaluated using available information. To determine the probability of particular public health events, the risk of importation and risk of transmission were taken into consideration. KCDC used 5 levels ("very low," "low," "moderate," "high," and "very high") for each category and overall risk was eventually decided.

Results: A total of 8 risk assessments were performed on 8 separate occasions between January 8 to February 28, 2020, depending on the detection and report of COVID-19 cases in other countries. The overall risk of the situation in each assessment increased in severity over this period: "low" (first), "moderate" (second), "high" (third), "high" (fourth), "high" (fifth), "high" (sixth), "high" (seventh), and "very high" (eighth).

Conclusion: The KCDC's 8 risk assessments were utilized to activate national emergency response mechanisms and eventually prepare for the pandemic to ensure the containment and mitigation of COVID-19 with non-pharmaceutical public health measures.
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http://dx.doi.org/10.24171/j.phrp.2020.11.2.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104687PMC
April 2020

Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial.

Blood 2020 06;135(24):2137-2145

Laiko General Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.

Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
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http://dx.doi.org/10.1182/blood.2020004856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290090PMC
June 2020

Limited Positive Predictive Value of β-d-Glucan in Hematologic Patients Receiving Antimold Prophylaxis.

Open Forum Infect Dis 2020 Mar 12;7(3):ofaa048. Epub 2020 Feb 12.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Diagnostic value of β-d-glucan (BDG) in populations with low prevalence of invasive fungal infection (IFI), such as hematologic patients receiving antimold prophylaxis, should be re-evaluated.

Methods: We retrospectively reviewed episodes with BDG results in hematologic patients receiving antimold prophylaxis from January 2017 to August 2019 in a tertiary hospital. The episodes were classified as true positive ([TP] positive BDG with IFI), true negative ([TN] negative BDG without IFI), false positive ([FP] positive BDG without IFI), false negative ([FN] negative BDG with IFI), and nonevaluable.

Results: A total of 203 episodes were analyzed: 101 episodes (49.8%) were from stem cell transplants, 89 (43.8%) were from induction chemotherapy, and 13 (6.4%) were from graft-versus-host disease treatment. There were 62 nonevaluable episodes. Among 141 evaluable ones, there were 8 (5.7%) episodes of probable/proven IFI. True positive, TN, FP, and FN cases were 4 (2.8%), 112 (79.4%), 21 (14.9%), and 4 (2.8%) episodes, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value were 50.0%, 84.2%, 16.1%, and 96.5%, respectively. Positive predictive value was 26.7% and 0.0% in diagnostic and surveillance episodes, respectively.

Conclusions: β-d-glucan test should be used to exclude IFI rather than for diagnosis in these patients.
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http://dx.doi.org/10.1093/ofid/ofaa048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051035PMC
March 2020

Importance of Monitoring Physical Function for Quality of Life Assessments in Hematopoietic Stem Cell Transplantation Patients: A Prospective Cohort Study.

In Vivo 2020 Mar-Apr;34(2):771-777

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea

Background/aim: Physical function is known to decrease after hematopoietic stem cell transplantation (HSCT), with the most substantial impairment noted at 90 days post-transplantation. Little is known about the natural course of physical function during the acute post-transplant period preciously. The aim of the study was to monitor the changes in physical function through serial evaluations of the physical function, and identify the effect of physical function on QoL during the acute post-transplant period.

Patients And Methods: This prospective cohort study included 41 patients admitted for planned autologous or allogeneic HSCT. Physical impairment was evaluated with decrease in the de Morton Mobility Index (DEMMI) every week and defined as a DEMMI score of more than 2 points after HSCT. The outcome variables for QoL included visual analogue scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrollment and discharge.

Results: Based on DEMMI scores, 24.40% of all HSCT patients showed physical impairment, for whom the DEMMI score showed an overall decrease during hospitalization with significant differences in scores at 1, 2, and 3 weeks after HSCT, between 1 week before and 3 weeks after HSCT, and between 1 and 3 weeks after HSCT. There was no significant difference of VAS between admission and discharge between the groups. Each functional subscale of EORTC QLQ-C30 differed significantly between the groups, with lower scores in the physical impairment group. There was only a significant difference in SDS at discharge between the groups. QoL pre-transplantation can be a predictive factor for physical impairment during the acute post-transplant period, which can be detected in the early period after HSCT.

Conclusion: Patients during acute post-transplant period had physical impairment and QoL of pre-transplantation was considered a predictive factor for physical impairment. The physical impairment can be detected in the early period after HSCT. Therefore, monitoring of standardized functional outcome measures is important to prevent physical impairment following HSCT.
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http://dx.doi.org/10.21873/invivo.11837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157879PMC
November 2020
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