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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR-CD14+ monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we identified, using high-throughput screening, a set of surface markers that are strongly expressed in HLA-DR-CD14+ monocytic MDSCs isolated from the peripheral blood (PB) of patients receiving allo-HSCT. Subsequent experiments showed the consistent dominant expression of CD1d in monocytic MDSCs of allo-HSCT PB in comparison with granulocytic MDSCs. In addition, CD1d-expressing cells isolated from PB of allo-HSCT patients showed the suppressive activity of T cell proliferation and higher expression of MyD88 and IDO compared with CD1d- cells. Our results suggest that CD1d could be a valuable marker for further therapeutic evaluation of human monocytic MDSCs for immune-related diseases, including GVHD.

Introduction Daratumumab, a human IgG monoclonal antibody targeting CD38, has demonstrated activity as monotherapy and in combination with standard-of-care regimens in multiple myeloma. Population pharmacokinetic analyses were conducted to determine the pharmacokinetics of intravenous daratumumab in combination therapy versus monotherapy, evaluate the effect of patient- and disease-related covariates on drug disposition, and examine the relationships between daratumumab exposure and efficacy/safety outcomes. Methods Four clinical studies of daratumumab in combination with lenalidomide/dexamethasone (POLLUX and GEN503); bortezomib/dexamethasone (CASTOR); pomalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone, and bortezomib/melphalan/prednisone (EQUULEUS) were included in the analysis. Using various dosing schedules, the majority of patients (684/694) received daratumumab at a dose of 16 mg/kg. In GEN503, daratumumab was administered at a dose of 2 mg/kg (n = 3), 4 mg/kg (n = 3), 8 mg/kg (n = 4), and 16 mg/kg (n = 34). A total of 650 patients in EQUULEUS (n = 128), POLLUX (n = 282), and CASTOR (n = 240) received daratumumab 16 mg/kg. The exposure–efficacy and exposure–safety relationships examined progression-free survival (PFS) and selected adverse events (infusion-related reactions; thrombocytopenia, anemia, neutropenia, lymphopenia, and infections), respectively. Results Pharmacokinetic profiles of daratumumab were similar between monotherapy and combination therapy. Covariate analysis identified no clinically important effects on daratumumab exposure, and no dose adjustments were recommended on the basis of these factors. Maximal clinical benefit on PFS was achieved for the majority of patients (approximately 75%) at the 16 mg/kg dose. No apparent relationship was observed between daratumumab exposure and selected adverse events. Conclusion These data support the recommended 16 mg/kg dose of daratumumab and the respective dosing schedules in the POLLUX and CASTOR pivotal studies. Funding Janssen Research & Development. Electronic supplementary material The online version of this article (10.1007/s12325-018-0815-9) contains supplementary material, which is available to authorized users.

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

Background Plasmacytoma at the time of relapse of multiple myeloma is associated with poor response and survival. However, data on the activity of the recently available new drug or drug combinations in RRMM with plasmacytoma in the real-world clinical practice is limited. Pomalidomide and dexamethasone (Pd) with or without cyclophosphamide is an active therapeutic combination in relapsed and refractory multiple myeloma (RRMM) after 2 lines of previous line of therapy Method This study aimed to analyze the clinical outcome of the pomalidomide-based regimen in RRMM with plasmacytoma. Clinical data of 221 patients who were treated with Pd with or without cyclophosphamide from 7 hospitals participating in the Korean multiple myeloma working party were retrospectively analyzed by electronic medical chart review. All the of patients were previously treated with at least 2 lines of therapies including bortezomib and lenalidomide in most of the patients. Plasmacytoma was diagnosed by the computed tomography, magnetic resonance imaging or FDG-PET scan Result Twenty-nine patients among the 221 patients analyzed (13.1%) had plasmacytoma at the time of pomalidomide-based chemotherapy. Patients were previously treated with a median 4 lines of therapy (range, 2-14), including bortezomib, lenalidomide, autologous stem cell transplantation in 97%,100%, and 52% of the patients, respectively. 14 patients were treated with Pd and 15 patients had been treated with Pd and cyclophosphamide (PCd). Median number of sites of plasmacytoma involvement was 2 (range, 1-9), including paraskeletal and soft tissue involvement in 83% and 52% of the patients. Sites of soft tissue involvement were: 5 pleura, 4 lymph nodes, 4 subcutaneous, 3 liver, 3 muscle, 2 pancreas, 1 kidney, 1 pericardium, 1 peritoneum, 1 adrenal gland, and 1 stomach. 50% patients (13 among the 26 response evaluable patients) had responded to Pd with or without Cy: 2 complete response, 2 very good partial response, 9 partial response, 1 stable disease, 2 minimal response, and 10 progressive disease. Patients who were treated with PCd showed a better response compared with Pd therapy (53% versus 29%, P=0.264). After a median follow-up of 9.33 months (range, 0.30-52months), patients with plasmacytoma versus no plasmacytoma showed a progression-free survival of 3.57 (95% CI, 0.35-6.78 months) versus 8.40 months (95% CI, 7.00-9.80 months) (P=0.002) and an overall survival of 3.33 (95% CI, 0.00-7.82 months) versus 19.67 months (95% CI, 13.39-25.95 months) (P=0.001). Conclusion RRMM patients with plasmacytoma was responsive after pomalidomide-based chemotherapies. The addition of cyclophosphamide to Pd seemed to result in a better response compared with Pd only. However, RRMM patients with plasmacytoma had poorer survival compared with patients without plasmacytoma even after Pd with or without cyclophosphamide.

Background A high number of focal lesions (FL) detected using PET/CT at diagnosis were found to be associated with adverse prognosis along with Revised International Staging System (R-ISS). In present study, we combined R-ISS with FL using PET/CT to design a reliable and easily applicable risk stratification system in patients with newly diagnosed MM (NDMM). Methods In training cohort, the data of 380 patients with NDMM who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis from 10 hospitals of the Korean Multiple Myeloma Working Party were retrospectively analyzed. All patients were classified by R-ISS and were treated by frontline therapy with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD). The K-adaptive partitioning algorithm was adopted to develop the new risk groups with homogeneous survival. Sixty-seven patients in external validation cohort were additionally collected to confirm reproducibility of the new risk groups. Results In the training cohort, 199 patients (52.4%) showed FL > 3 using PET/CT at diagnosis. R-ISS stages I, II, and III were 78 patients (20.5%), 230 (60.5%), and 72 (18.9%), respectively. The combined R-ISS with PET/CT newly allocated NDMM patients into four groups: R-ISS/PET stage I (n=30; R-ISS I with FL≤3), stage II (n=149; R-ISS I with FL>3 and R-ISS II with FL≤3), stage III (n=166; R-ISS II with FL>3 and R-ISS III with FL≤3), and stage IV (n=35; R-ISS III with FL>3). The new R-ISS/PET showed significantly pronounced survival differences according to stages. Two-year overall survival (OS) rates were 96.6%, 89.5%, 75.0%, and 57.9% (p Conclusion The new R-ISS/PET had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.

The hard X-ray free-electron laser at the Pohang Accelerator Laboratory (PAL-XFEL) in the Republic of Korea achieved saturation of a 0.144 nm free-electron laser beam on 27 November 2016, making it the third hard X-ray free-electron laser in the world, following the demonstrations of the Linac Coherent Light Source (LCLS) and the SPring-8 Angstrom Compact Free Electron Laser (SACLA). The use of electron-beam-based alignment incorporating undulator radiation spectrum analysis has allowed reliable operation of PAL-XFEL with unprecedented temporal stability and dispersion-free orbits. In particular, a timing jitter of just 20 fs for the free-electron laser photon beam is consistently achieved due to the use of a state-of-the-art design of the electron linear accelerator and electron-beam-based alignment. The low timing jitter of the electron beam makes it possible to observe Bi(111) phonon dynamics without the need for timing-jitter correction, indicating that PAL-XFEL will be an extremely useful tool for hard X-ray time-resolved experiments. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) in South Korea has now entered operation with a timing jitter of just 20 fs.

Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute GVHD (hazard ratio [HR], 2.902; 95% confidence interval [CI], 1.417 to 5.942; P = .004), chronic GVHD (HR , 3.005; 95% CI, 1.279 to 7.059; P = .012), and GFFS (HR, 2.363; 95% CI, 1.162 to 4.805; P = .014). Toxicities, including infectious complications, were not different among the 3 groups. In conclusion, low-dose ATG (2.5 mg/kg) can reduce the incidence of acute and chronic GVHD and improve the quality of life in patients with SAA who receive stem cells from either an HLA-mismatched donor or PB; importantly, these benefits are achieved without increased toxicity. Furthermore, ATG can be considered in URD SCT from HLA-matched BM cells.

This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide 18F (18F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4-76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1st progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1st progression, which translated into poor OS, providing insight into the different biological effect of ELs.

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone. Overall response rates after initial therapy were significantly higher in patients treated with novel agent-based regimens compared with those treated with conventional chemotherapies (75% vs. 43.4%, P = 0.026). Median progression-free survival (PFS) and overall survival (OS) were 12.2 months and 16.1 months, respectively. The median PFS of the four treatment groups–conventional chemotherapy alone, novel agents alone, conventional chemotherapy with ASCT, and novel agents with ASCT–were 1.2, 9.0, 10.5, and 26.4 months, respectively (P < 0.001); the median OS of the four treatment groups were 2.9, 12.3, 14.1, and 31.1 months, respectively (P < 0.001). The median OS was also significantly better in the patients with novel agents with ASCT versus other patients. In a multivariate analysis, an increased lactate dehydrogenase level, low albumin (< 3.5 g/dL), and non-CR after front-line treatment were independently associated with poor PFS and OS. In conclusion, the use of novel agent-based therapy with ASCT and achieving a deep response to front-line treatment are important in expecting improved PFS and OS in patients with pPCL.

Objective Short tandem repeat (STR) loci are most frequently used for chimerism analysis after hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the practical informativeness of STR chimerism by integrating theoretical and analytical points. Methods Theoretical and practical informativess of 16 STR loci were evaluated from 1249 pairs of recipients and donors who were prepared for HSCT. Results Theoretical informativeness was influenced by genetic diversity including allele frequency and heterozygosity, and was higher in the unrelated HSCT group (90.5 ± 5.3%) compared to the related HSCT group (66.2 ± 4.4%). Practical informativeness was lower than theoretical (6.1 ± 1.7%) because several STR loci were excluded due to stutter peaks and less reliable results, especially in type II-2 donor-recipient match pattern with no recipient-specific allele. We simulated an efficient STR combination for reliable chimerism analysis. Eight informative STR loci were required to analyze chimerism with at least one practically informative locus in the related HSCT group (D18S51, FGA, D2S1338, D13S317, D8S1179, D21S11, D16S539 and D7S820) while only three loci were needed in the unrelated group (D2S1338, FGA and D18S51). A minimum set of 2, 4 or 7 STR loci were required to provide at least 1, 3 or 5 practically informative loci in 95% of the unrelated HSCT group while 3, 8 or 12 loci were required in the related HSCT group. Conclusion We deducted the practical informativeness of STR chimerism, identified the major influencing factors on the practical informativeness of each STR locus, and successfully simulated the efficient STR combination for reliable chimerism analysis.

The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34+ stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m2), and melphalan (100 mg/m2). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1, high dose of CD34+ stem cell (≥4.5 × 106/kg) infusion, and c-kit or FLT3-ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1, multivariate analysis revealed that patients with young age (

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

Background Maintenance therapy improves PFS in NDMM pts. Additional active, well-tolerated treatment options that are suitable for long-term administration are required. The international, multicenter, double-blind, placebo-controlled, phase 3 TOURMALINE-MM4 trial (NCT02312258) of the oral PI ixazomib as maintenance therapy post-induction in non-transplant NDMM pts met its primary endpoint of PFS. Ixazomib demonstrated a significant and clinically meaningful benefit vs placebo, with a manageable and well-tolerated toxicity profile. Feasible, tolerable options for long-term therapy are particularly important in this setting, as pts are often elderly and/or frail. We report herein a subgroup analysis of TOURMALINE-MM4 according to age and frailty status. Methods Pts who achieved ≥partial response (PR) after 6-12 months of standard-of-care induction therapy were randomized 3:2 to ixazomib or placebo maintenance for up to 24 months. The sum of 4 components - age (80 years; score 0 vs 1 vs 2), the Katz Index of Independence in Activities of Daily Living (ADL; >4 vs ≤4, score 0 vs 1), the Lawton Instrumental ADL Scale (>5 vs ≤5, score 0 vs 1), and the Charlson Comorbidity Index (≤1 vs ≥2, score 0 vs 1) - was used to classify pts as fit (total score: 0), unfit (score: 1), or frail (score: ≥2). Analyses of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and MY20 modules were conducted to evaluate the effects of treatment on QoL within subgroups defined by frailty status and age. Results In the ixazomib (n=425) vs placebo (n=281) arms, there were similar proportions of pts aged PFS benefit with ixazomib vs placebo was seen across age groups, with hazard ratios (HRs) of 0.576 (95% confidence interval [CI] 0.299-1.108, p=0.095, median 11.0 vs 9.3 months) in pts aged Rates of grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuation due to TEAEs were higher or similar with ixazomib vs placebo across age and frailty subgroups (Table 2). Rates were generally somewhat higher in older age groups and in unfit/frail pts in both arms; nevertheless, rates of discontinuation due to TEAEs across groups were Covariate-adjusted changes in QoL subscales from baseline were estimated at each cycle using repeated measures linear mixed models stratified by frailty status. In all frailty groups, the mean changes in each treatment arm were small over time ( Conclusions Ixazomib as post-induction maintenance therapy in non-transplant NDMM pts results in PFS benefits vs placebo regardless of age or frailty status. Ixazomib appeared generally well tolerated across groups, with TEAE rates in both arms generally elevated in elderly/frail vs younger/fit pts. Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous pt population. Disclosures Bringhen: Takeda: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Vorog:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Labotka:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Wang:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Cherepanov:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Cain:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Manne:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Dimopoulos:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Beigene: Honoraria; Amgen: Honoraria. OffLabel Disclosure: Use of the oral proteasome inhibitor ixazomib as maintenance therapy in patients with newly diagnosed multiple myeloma not undergoing stem cell transplantation

Background and Aims: The Asia-Pacific (APAC) Myeloma and Related Diseases Registry (MRDR) collects data on epidemiology, treatment and outcome trends for patients with multiple myeloma (MM) in participating regional countries. Prevalence of MM is expected to continue to increase with ageing populations and improvements in survival. Although some MM data are available for Asia, very few exist at regional level. Generation of 'real world evidence' on practice and outcomes is important to complement data from clinical trials. In the APAC MRDR, regional clinical experts provide local clinical context and registry oversight, and participating hospitals obtain local ethics approval and manage patient recruitment and data collection. Methods: The APAC MRDR prospectively collects observational data on patient characteristics, diagnosis, medical history, treatment (including supportive therapies), and outcomes (overall and progression-free survival, and quality of life using the EQ-5D-5L) on newly diagnosed MM (NDMM), plasma cell leukaemia, plasmacytoma, and MGUS patients via a secure, country-specific, web-based database. Participants are reviewed 4-monthly for a minimum of 2 years. Preliminary data from October 2018 to June 2020 were analysed. Results: 20 hospitals have ethics approval to participate and patient recruitment has commenced at 14 hospitals in Korea, Singapore, and Malaysia. Sites in Taiwan will also start recruitment in 2020, and sites in China have been identified. To date, a total of 469 patients (419 NDMM) have been enrolled, of which, data from 348 (83%) NDMM participants from Korea, Singapore, and Malaysia were available for analysis. Results are presented in Table 1. Summary and Conclusions: The APAC MRDR is now successfully established and expanding. As data mature, these will provide important new information on the epidemiology and treatment of MM across the APAC region, and provide opportunities for regional benchmarking and collaborative research. Disclosures Spencer: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Secura Bio: Consultancy, Honoraria; Pharmamar: Research Funding; Roche: Honoraria; Servier: Consultancy, Honoraria, Research Funding; HaemaLogiX: Consultancy, Honoraria, Research Funding.

Introduction Acute myeloid leukemia (AML) has been considered as a hematological emergency. However, debates on how much the time from diagnosis to treatment (TDT) can be justified to choose the optimal treatment in AML have been raised due to the increased possibility of customized treatment with novel targeted agents based on genetic abnormalities tested by newly applicable diagnostic tools. Three recent studies with a large data set from Western countries showed conflicting results about the relationship between TDT and prognosis. Thus, we evaluated the influence of TDT on patients' outcomes from a large data set of Asian patients. Methods We retrospectively evaluated a cohort of AML patients aged 18 and older who visited the Catholic Hematology Hospital in Korea and received anthracycline-based intensive chemotherapy from 2002 to 2016. A total of 1313 patients were included in this analysis, of which 1282 were used for analysis, excluding 26 patients with incomplete documentation and with more than 90 days of TDT. Patients under the age of 60 (Young group, YG) and patients over 60 years of age (Elderly group, EG) were analyzed as an individual cohort. In both cohorts, the effects of TDT on complete remission (CR/CRi), early death (ED), and overall survival (OS) were analyzed. The TDT was analyzed as a continuous variable to minimize the loss of information, while also grouped into four ordinal groups of 1-5, 6-10, 11-15, and 16- to visualize data and find appropriate cutoff. In order to adjust for the influence of established prognostic variables on the outcomes, we used multivariate regression models. In both univariate and multivariate analyses, the transformation of variables or relaxing the linearity such as restricted cubic splining (RCS) were considered to reflect the data properly and not to violate the model assumptions. When TDT was treated as an ordinal variable, the effects of TDT on CR/CRi and ED were evaluated by Cochran-Armitage trend tests, and the effect on OS was checked by the log-rank test. Results Median age of YG (n=1104) and EG (n=178) were 40 years (interquartile range, IQR; 32-49) and 63 years (IQR; 61-64), respectively. Median TDT of both groups was 8 in days (IQR; 6-11 in YG and 6-13 in EG). When TDT was categorized into 4 groups, patients with higher WBC count tended to belong to earlier TDT groups in both YG and EG cohorts, and secondary AML patients were more placed in the later TDT groups especially in YG cohort. Univariate analyses of TDT in YG showed that TDT had significant correlation with CR/CRi rate, ED rate, and OS. Odds ratio (OR) of CR/CRi per one day treatment delay was -0.0206 (95% CI; -0.0412~-0.0000), and OR of ED per one day delay was 0.0439 (95% CI; 0.0126~0.0752) (Table 1 and Figure 1). RCS method was applied on OS model, so a single value of the hazard ratio (HR) per one day treatment delay was not available, but we could say HR of patients of TDT 2 versus (vs.) patients of TDT 16 was 0.6063 (95% CI; 0.4450-0.8259) in our model (Figure 2). Even after TDT was treated as a grouped variable, TDT was still significant on the ED rate and OS in YG. Especially, High ED rate and low 2-year OS of a group of TDT more than 15 days were noticed (Table 1). In EG, there was no significant effect of TDT on all patients' outcomes (Table 1). Multivariate analyses including age, WBC, AML type, MRC risk, and HSCT status showed that, in YG, TDT effect on CR/CRi rate turned to be insignificant, but TDT still acted as a significant variable for ED and OS. In EG, there was no significant effects of TDT on ED and OS, as like univariate analyses. When the treatment course was divided into 'during induction', 'between induction and HSCT', and 'after HSCT' in YG, there was no significant difference in the rate of death between TDT groups except for the deaths during the induction period (Table 3 and Figure 3). Conclusion Our data revealed the effects of TDT on OS and ED in YG, which were significant in multivariate analyses adjusting the effects of other variables. When the timing of death was divided in YG, the only ED was significantly different between TDT groups, especially in the group with more than 15 days of TDT. These results suggest that TDT matters in YG and delayed initiation of treatment over 15 days after diagnosis would increase risk of early mortalities. On the other hand, little effects of TDT on EG provide a rational for sufficient evaluation of comorbidity and functional impairments to select appropriate initial treatment. Disclosures Kim: Takeda: Research Funding; ILYANG: Consultancy, Honoraria, Research Funding; Sun Pharma.: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kim:Abbvie: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Genzyme: Honoraria; SL VaxiGen: Consultancy, Honoraria; Yuhan: Consultancy, Honoraria; AML Global Portal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astella: Consultancy, Membership on an entity's Board of Directors or advisory committees; BL&H: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

To reduce inter-implant metal artifacts in cone-beam CT (CBCT) imaging by adjusting angular position of the subject relative to the source–detector plane. Two dental implants were placed in a block made of homogeneous dental impression material. Using a custom-made apparatus, the specimen was scanned with a CBCT machine at seven different angles (0°, 15°, 30°, 45°, 60°, 75°, and 90°) along three different spatial axes, yielding 21 experimental groups. Thirteen volumes of interest (VOI) including inter- and peri-implant areas were selected from each axial reconstruction perpendicular to the implants. Gray values (GVs) of each pixel within these VOIs were measured. Mean differences in GV (ΔGV) between the VOIs and control area were calculated and expressed as a percentage. These ΔGVs from different spatial angle were compared and analyzed by Welch’s analysis of variance (ANOVA) and linear regression using SPSS 25.0 software. As alpha angle increased, the ΔGV of the inter-implant area increased from − 62.02% to near-zero while the standard deviation decreased. Welch’s ANOVA and linear regression analysis revealed ΔGV increased significantly with alpha angle (p

Background: Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents. Methods: A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes. Results: The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression ( n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd ( n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) ( p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039). Conclusions: In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.

© The Author(s)., Background: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). [Methods]: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. [Results]: After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. [Conclusion]: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. Trial registration: ClinicalTrials.gov, NCT02136134. Registered 12 May 2014, This CASTOR study was sponsored by Janssen Research & Development, LLC. Open access funding provided by Projekt DEAL.

Additional file 1. Supplementary methods and figure.

The hard XFEL operation procedure established at PAL-XFEL using e-BBA and incorporating undulator radiation spectrum analysis proved to be highly reliable and robust, and essential for the variable-gap undulators. The state-of-the-art design of the electron linear accelerator along with the reliable FEL lasing procedure has allowed reliable operation of PAL-XFEL with unprecedented stability in terms of orbit, energy, and timing; FEL position stability: 8 ~ 9% of beam size, FEL power stability: ~ 4.0% rms, FEL timing jitter: < 20 fs, which can obviously make users’ experiments more successful. And the undulator optics matching using the wire-scanner-based emittance measurement is extensively used to maximize the FEL intensity even at higher photon energy up to 14.5 keV, which is the brightest FEL at this photon energy that has ever been achieved in the world.

OBJECTIVE We investigated the role of anti-thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). METHODS Forty-seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no-ATG group; median age 43, P

The recent improvements in the outcomes of severe aplastic anemia (SAA) patients who received allogeneic stem cell transplantation (SCT) from unrelated donors (URD) suggest the possibility of its alternative first-line treatment. To address this issue, results of adult SAA patients receiving allogeneic SCT were compared between the following three donor-type groups: 8/8–matched sibling (MSD; n = 153), 8/8 well-matched unrelated (WM-URD; n = 72), and 6–7/8 partially matched unrelated (PM-URD; n = 33). Proportion of patients who experienced immunosuppressive treatment failures was significantly higher in the URD groups than in the MSD group (P

We explored prognostic roles of circulating microRNAs (miRs) in multiple myeloma (MM) treated with autologous stem cell transplantation (ASCT) following induction chemotherapy. In part I of the study (n = 40), we identified a decreasing dynamics of circulating miR-193a-5p expression from diagnosis to pre-ASCT. In patients who experienced early relapse within one year post ASCT (n = 9) these patterns were distinctive compared to those without early relapse in a 1:2 matched cohort (n = 18). In part II (n = 90), multivariate analyses showed that the International Staging System score and miR-193a-5p expression before ASCT were independent prognostic factors. Conclusively, expression of circulating miR-193a-5p before ASCT could be a prognostic biomarker for transplant-eligible MM.

In this study, we investigated the safety and efficacy of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The patients had been classified as unfit to receive anthracycline-based chemotherapy due to high-risk factors for early death. Twenty-five patients with APL receiving ATO/ATRA between 2007 and 2018 were divided into 3 groups as follows: elderly patients (age ≥ 70 years) with poor performance status (32%); patients with severe active infections at diagnosis (56%); and patients with multiple significant comorbidities (24%) who were unfit for conventional chemotherapy, regardless of age. Induction therapy comprised 0.15 mg/kg/day ATO combined with 45 mg/m2/day ATRA until patients attained complete remission (CR). Notably, only one patient (4.0%) died of septic shock 2 days after the ATO treatment had been initiated. The remaining 24 patients attained CR despite their serious and desperate conditions at diagnosis. In total, 44%, 28%, and 32% of the patients experienced neutropenia (grade 3 or 4), thrombocytopenia, and hepatopathy, respectively. Twenty-three of the 24 patients in CR proceeded to consolidation therapy and attained complete molecular remission with favorable overall survival (90.7%). This study demonstrates the safety and efficacy profile of ATO/ATRA first-line therapy for patients with APL and high-risk features for early death.

Background For patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM). Patients and Methods We conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide. Results In 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities. Conclusion Thalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.

The absence of relevant guidelines for Wilms tumor 1 (WT1) gene quantification as a measurable residual disease (MRD) assessment for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has limited the widespread use in practice. We investigated optimal time points, thresholds, and candidates for the bone marrow WT1 MRD assay in 425 consecutive patients with AML who underwent allo-HSCT. WT1 expression kinetics before allo-HSCT and at 1 or 3 months after allo-HSCT were determined by real-time PCR using the European LeukemiaNet (ELN) normalized method. Relapsed patients had significantly higher WT1 levels before allo-HSCT and at 3 months after allo-HSCT. The best time point for the WT1 MRD assay was before allo-HSCT by the receiver operating characteristic curve. Among various thresholds, 250 copies recommended from ELN researchers were mostly predictive of post-transplant relapse. In multivariate analysis, WT1 MRD positivity independently predicted relapse, resulting in inferior survival. In subgroup analyses, pretransplant WT1 MRD positivity was predictive of post-transplant relapse in the intermediate group, whereas WT1 MRD positivity occurred at 3 months after allo-HSCT in favorable and adverse risk groups. Among MRD-positive patients before allo-HSCT, all patients who were MRD positive at 3 months relapsed within 6 months. The WT1 MRD assay before allo-HSCT or 3 months after allo-HSCT is useful for predicting post-transplant relapse with a different significance in each risk group by time points, showing the benefit of multiple tests over time. Such monitoring is particularly available in patients with AML without specific molecular targets.

Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT). Here, we report a rare case of GVHD involving the central nervous system (CNS). A 35-year-old woman was diagnosed with myelodysplastic syndrome unclassifiable and underwent allogeneic peripheral blood SCT for disease progression to myelodysplastic syndrome with excess blasts-2. One year following SCT, she experienced chronic oral and hepatic GVHD symptoms, which were managed with oral steroids and tacrolimus. Sixteen months after SCT, she developed sudden-onset, generalized, tonic–clonic-type seizures. Magnetic resonance imaging and cerebrospinal fluid evaluation showed multiple discrete white lesions and elevated IgG levels. Brain biopsy revealed periventricular plaques with the destruction of axons, representing a demyelinating disease of the CNS. We diagnosed the case as CNS GVHD. Neurologic symptoms gradually improved with methylprednisolone pulse therapy and total plasma exchange combined with a calcineurin inhibitor; the brain lesions nearly disappeared after decreasing steroid maintenance dosage, and were completely resolved 1 year after the onset of CNS GVHD. The patient is CNS GVHD-symptom-free, 3-year post-transplantation. Thus, CNS GVHD should be considered in cases of newly developed neurologic symptoms in SCT recipients showing evidence of preceding chronic GVHD.

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

The PAL-XFEL has a 716m hard X-ray linac and a soft X-ray linac. There are 51 modulators, 178 accelerators structures, and the pulse energy doublers in the linac. The construction was completed at the end of 2015. After RF-conditioned for one year in 2016, The machines provide to the user service in 30Hz, $\pmb{4\mu} \mathbf{s}$ on hard x-ray. The pulse energy doubler is one of the important devices that increases the peak output power of the 2.856 GHz high frequency generated by the Klystron. The device receives a $\pmb{4\mu}\mathbf{s}$ length for high frequency power from the klystron and reduces the length of the pulse output to Iμs, However, the maximum peak output power can be increased four times. The total of 42 pulsed energy doublers are installed in the PAL XFEL RF system. It consists of two resonators and one 3dB coupler. The amount of heat generated depends on the operation repetition frequency. There are two ways to prevent it. Change the water temperature of the cavity cooling system or adjust the volume of each resonator. We installed a system that can remotely adjust the resonator volume by connecting a motor to each resonator. This paper reports the results of tuning at 30Hz. We also experimented a few to prepare for 60Hz operation. It reports the results of adjusting the resonance frequency by changing the volume and the cavity cooling temperature using a remote cavity tuning system.

The construction of Pohang Accelerator Laboratory X-ray Free Electron Laser(P Al-xfel)was completed by the end of 2015. Acceleration modules used in the 4th generation electronic acceleration are 51 modules including Hard X-ray and Soft X-ray. Among the high power pulse power devices used as energy source for accelerating electrons in the 4th generation linear accelerator, the beam is being supplied to the user in 30 Hz, 4uS, SLED tune mode of the 49sets module installed in the hard X-ray. The PAL-XFEL needs a highly stable electron beam. The very stable beam voltage of a klystron-modulator is essential to provide the stable acceleration field for an electron beam. Thus, the modulator system for the XFEL requires less than 50 ppm beam voltage stability. To get this high stability on the modulator system, the inverter type HVPS is a pivot component. And the modulator needs lower noise and more smart system. The commissioning began in April 2016, and the lasing of the hard X-ray FEL was achieved on end of 2016. Beginning to provide users with beams from 2017, we will present the operating status of the Klystron-modulator when providing beams to users in 2018.

Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently receive empiric antibiotics during the neutropenic period before engraftment. Several recent studies have shown that anaerobes in the intestine are important mediators of intestinal homeostasis, and that commensal bacteria can be potent modulators of the severity of acute graft-versus-host disease (aGVHD). However, the relationships among the type of antibiotic used during the neutropenic period, changes in the intestinal microbiota, and subsequent occurrence of aGVHD are not clear. In this study, a total of 211 patients undergoing HSCT were stratified into 3 groups: patients not treated with any antibiotics during the neutropenic period (group 1; n = 43), patients treated with cefepime only (group 2; n = 87), and patients treated with carbapenem antibiotics, defined as meropenem or prepenem with or without previous cefepime therapy (group 3; n = 81). Intestinal microbiota analyses were performed on pre- and post-HSCT stool samples, and immunophenotypic analyses were performed on pre- and post-HSCT peripheral blood samples. Among the 211 patients, 95 (45%) developed aGVHD (grade ≥II), including 54 with intestinal GVHD. The incidence of intestinal GVHD was higher in group 3 compared with group 1 and group 2 (32.1%, 11.6%, and 26.4%, respectively; P = .044). After adjusting for potentially significant variables identified by univariate analysis, multivariate analyses identified broad-spectrum antibiotic use during the neutropenic period as associated with the occurrence of intestinal GVHD (hazard ratio, 3.25; 95% confidence interval, 1.13 to 9.34; P = .029). Accordingly, loss of bacterial diversity in terms of alterations in intestinal microbiota after HSCT was observed in patients who received broad-spectrum antibiotics. Moreover, alterations in the frequencies of several intestinal bacteria phyla were associated with the occurrence of intestinal GVHD. Evaluation of circulating immune cell subsets according to type of antibiotic used during the neutropenic period revealed delayed recovery of myeloid-derived suppressor cells in the broad-spectrum antibiotic use group. Our data indicate that the use of broad-spectrum antibiotics during the neutropenic period is associated with a higher incidence of intestinal GVHD via loss of microbiome diversity. Further studies are needed to determine whether maintaining bacterial diversity can help prevent the development of aGVHD.

Background The aim of this study is to evaluate the prognostic impact of myeloid-derived suppressor cells (MDSCs) in multiple myeloma (MM) in the context of autologous stem cell transplantation (ASCT). Methods Peripheral blood samples were collected for measuring monocytic (M-) MDSCs (CD14posHLA-DRlow/neg) and early-stage (E-) MDSCs (LinnegHLA-DRnegCD33posCD11bpos) before and after ASCT. Clinical outcomes following ASCT differed according to the frequency of each MDSC phenotype. Results In the pre-ASCT analyses, lower M-MDSCs (

X-ray free electron lasers (XFELs) require electron beams with a peak current of several kA and a transverse emittance below 1 mm mrad. The uncorrelated energy spread of the beam should be as small as 0.01% of the beam energy. A photoinjector generates an electron beam satisfying the requirements, however the uncorrelated energy spread of the beam is too small, about one keV. A beam with such a low uncorrelated energy spread may suffer from the longitudinal microbunching instability when the beam is accelerated and compressed through a linear accelerator. A laser heater system in the injector minimizes the microbunching instability growth by controlling the uncorrelated energy spread of the beam. In this paper, we introduce the PAL-XFEL laser heater system and the commissioning result. The laser heating effects depending on the undulator gap, infrared laser pulse energy and laser beam size are studied. Experimental studies on the laser heating depending on the relative spatial position between the infrared laser and electron beam are discussed in detail.

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three‐hundred and seventy‐six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second‐line chemotherapy in 142 (37.8%) patients, and third‐line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression‐free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD.

Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice.

Allogeneic stem cell transplantation from HLA-matched siblings (MSD-SCT) for elderly patients with severe aplastic anemia (SAA) is not a widely accepted first-line treatment. Recently, fludarabine, lower-dose cyclophosphamide and antithymocyte globulin conditioning (Flu/lower-dose Cy/ATG) with lower toxicities has been investigated. To determine whether this regimen can overcome the negative effects of age, we analyzed 117 adult patients with SAA who received MSD-SCT using Flu/lower-dose Cy/ATG, and compared outcomes between 63 younger age group (YAG; ⩽40 years) and 54 older age group (OAG; >40 years) patients. No primary graft failure was observed. Neutrophil engraftment was significantly faster in the YAG compared with the OAG (12 vs 13 days; P=0.04). The incidences of acute grade II-IV (9.5% vs 9.3% at day 100; P=0.42) and chronic GVHD (8.1% vs 9.5% at 5 years; P=0.80), secondary graft failure (20.8% vs 7.9% at 5 years; P=0.11) and transplant-related mortality (5.4% and 11.1% at 5 years; P=0.91) were not significantly different between the YAG and OAG. In addition, failure-free (73.7% vs 81.0% at 5 years; P=0.73) and overall survival rates (93.7% vs 88.9% at 5 years; P=0.20) were comparable. Our results suggest that MSD-SCT using Flu/lower-dose Cy/ATG may be a feasible first-line treatment even in older patients with SAA.

Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy. Peripheral blood CD3(+), CD4(+), and CD8(+) cell frequencies were significantly decreased by 3 cycles of therapy, whereas NK cell frequency was significantly increased after the 3rd cycle. For the myeloid-derived suppressor cell (MDSC) subset, the frequency of granulocytic MDSCs transiently increased after the 1st cycle, whereas there was an increase in monocytic MDSC (M-MDSC) frequency after the 1st and 3rd cycles. Among 81 evaluable patients, failure to achieve a response of VGPR or greater was associated with a decrease in CD8(+) cell frequency and increase in M-MDSC frequency after 3 cycles of Len-dex treatment. A high proportion of natural killer T (NKT)-like cells (CD3(+)/CD56(+)) prior to Len-dex treatment might predict a longer time to progression. In addition, patients with a smaller decrease in the frequency of both CD3(+) cells and CD8(+) cells by 3 cycles exhibited a longer time to the next treatment. These results demonstrated that early changes in immune cell subsets are useful immunologic indicators of the efficacy of Len-dex treatment in RRMM.

The aim of this study was to evaluate the impact of pretransplant transfusion of packed red cells (PRCs) on outcome after allogeneic stem cell transplantation (SCT) in severe aplastic anemia (SAA). A total of 221 adult SAA patients receiving allogeneic SCT were analyzed. The patients were divided into two groups according to the amount of pretransplant transfusion before SCT: the low transfusion group (⩽32 PRC units, n=164) and the high transfusion group (>32 PRC units, n=57). The incidence of engraftment failure was not different between the two groups. The incidence of acute GvHD (grades II-IV) was higher in the high transfusion group than in the low transfusion group (P=0.04), and the incidences of chronic extensive GVHD were not significantly different (P=0.136). The high transfusion group had higher 5-year transplant-related mortality (TRM) (24.8% vs 6.8%, P

To understand the role of myeloid differentiation factor 88 (MyD88) expressed by donor bone marrow (BM) in the pathophysiology of graft-vs.-host disease (GVHD), we investigated the effects of transplantation of MyD88-deficient T cell-depleted BM (MyD88KO TCD-BM) on the severity of GVHD. Transplantation with MyD88KO TCD-BM aggravated GVHD; serious gut damage was evident, with high infiltration of T cells into the intestines of recipients and markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). MDSCs from MyD88KO mice were defective in inducing donor T-cell apoptosis and inhibiting T-cell proliferation. Supplementation of transplanted mice with MDSCs from wild-type mice, but not MyD88KO mice, attenuated GVHD severity with reduced intestinal T-cell infiltration in MyD88KO TCD-BM recipients. Pretreatment of BM donors with lipopolysaccharide to increase MDSC levels and MyD88 transcription in the TCD-BM transplant alleviated GVHD severity and intestinal T-cell infiltration. The T cell/MDSC ratios were correlated with intestinal GVHD severity in both animal models and human patients. This study indicates that MyD88-dependent MDSC expansion from donor BM is critical for protection against fatal intestinal GVHD.

In real clinical settings (not clinical trials), thalidomide has been accepted as maintenance therapy to patients with multiple myeloma (MM) because of the cost of drugs, the limitations of medical insurance, etc., in our country (South Korea). The purpose of this study was to evaluate the utility of thalidomide maintenance for improving survival in transplantation-eligible patients with MM in the real clinical field. Differences in survival rates were estimated in patients treated with or without thalidomide maintenance. The 3-year progression-free survival rates (PFS) of patients with and without maintenance, respectively, were 55.4 and 37.2 % (p = 0.005). The 3-year overall survival rates (OS) were 88.0 and 84.0 % (p = 0.105). No difference in 3-year OS after relapse or progression (OS2) was observed between the two groups (50.4 and 55.3 %, p = 0.661). The 3-year PFS of patients with and without maintenance therapy who had shown less than CR after ASCT were 68.4 and 23.3 % (p

BACKGROUND/AIMS Multiple myeloma (MM)-associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e' (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = -0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice consecutively, but GCV was sometimes delayed in patients without significant graft-vs-host disease (GVHD) by reducing immunosuppressive agents. In the entire group, CMV-reactivation showed poor overall survival (OS). To evaluate subsequent effects of CMV-reactivation, we excluded early relapse and deaths within 100 days, during which most of the CMV-reactivation occurred. Untreated CMV-reactivated group (n = 173) showed superior OS (83.8% vs. 61.7% vs. 74.0%, p < 0.001) with lower relapse rate (10.1% vs 22.1% vs. 25.5%, p = 0.004) compared to GCV-treated CMV-reactivated group (n = 122) and CMV-undetected group (n = 42). After excluding chronic GVHD, untreated CMV-reactivated group still showed lower relapse rate (9.4% vs. 24.1% vs. 30.2%, p = 0.006). Multivariate analysis showed adverse-risk karyotype and patients in other than untreated CMV-reactivated group were independent factors for relapse prediction. Our data showed possible GVL effect of CMV-reactivation and minimizing antiviral therapy may benefit for relapse prevention in acute leukemia.

Introduction: Systemic AL amyloidosis is a rare disorder of clonal CD38+ plasma cells characterized by deposition of insoluble amyloid fibrils leading to tissue damage and organ dysfunction. Currently, there are no health authority-approved treatments for AL amyloidosis, and standard of care (SoC) includes therapies developed for multiple myeloma (MM). DARA is a human CD38-targeting antibody for MM. Combining DARA with VCd improved outcomes for AL amyloidosis versus VCd alone in the phase 3 ANDROMEDA study. Here, we report a subgroup analysis of Asian patients (China, Japan, and Korea) from ANDROMEDA. Methods: Eligible patients had newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and no symptomatic MM. Patients were randomized 1:1 to receive DARA SC plus VCd (D-VCd) or VCd. All patients received bortezomib (1.3 mg/m2 SC QW), cyclophosphamide (300 mg/m2 PO or IV QW), and dexamethasone (40 mg PO or IV QW) for six 28-day cycles with or without DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]; ENHANZE® drug delivery technology, Halozyme, Inc.) by injection QW in Cycles 1-2, Q2W in Cycles 3-6; after Cycle 6, patients continued DARA monotherapy as maintenance for up to 24 cycles (28-day cycles). Disease status was evaluated Q4W in Cycles 1-6 and Q8W after Cycle 7 until hematologic progression or major organ deterioration. The primary endpoint was overall hematologic complete response (CR) rate; key secondary endpoints included major organ deterioration progression-free survival (MOD-PFS), survival, and safety. MOD-PFS was defined as the time from randomization to any of the following events (whichever occurred first): death, clinical manifestation of cardiac or renal failure, or hematologic progression. Results: Among 388 randomized patients (D-VCd, n=195; VCd, n=193), 60 were Asian (D-VCd, n=29; VCd, n=31). Baseline characteristics were well balanced between arms and consistent with the intent-to-treat population. The median age was 66 years, 70% and 58% had heart and kidney involvement, respectively, and 60% had ≥2 organs involved. Cardiac stage I, II and IIIA/B were 28%, 28%, and 43%, respectively. The median duration of treatment was 9.2 mo for D-VCd and 5.3 mo for VCd. Median follow-up was 9.4 mo. The overall hematologic CR rate was 59% for D-VCd and 10% for VCd (odds ratio, 13.2; 95% CI, 3.3-53.7; P Conclusion: The addition of DARA SC to VCd was superior to VCd alone in Asian patients, resulting in deeper hematologic responses and improved clinical outcomes, including MOD-PFS, with a safety profile consistent with the overall study population. These data support the use of D-VCd in Asian patients with newly diagnosed AL amyloidosis. Disclosures Suzuki: Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Takeda, Amgen, Janssen and Celgene: Consultancy; Bristol-Myers Squibb, Celgene and Amgen: Research Funding. Wechalekar:Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhou:Peking University First Hospital: Current Employment. Iida:Celgene: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; AbbVie: Research Funding; Merck Sharpe Dohme: Research Funding; Janssen: Honoraria, Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo:Amgen: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Karyopharm: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel/accommodations/expenses; Janssen: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel/accommodations/expenses. OffLabel Disclosure: To evaluate the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with AL amyloidosis.

Introduction: Increased understanding of the pathophysiology of multiple myeloma (MM) and the introduction of new drugs has led to considerable survival improvements in recent years. The International Myeloma Working Group consensus recently updated the definition for high-risk MM based on cytogenetic abnormalities. Moreover, the recent introduction of new therapeutic agents and the revision of insurance reimbursement policies have changed the clinical characteristics of MM patients in Korea. Yet, current epidemiology and the clinical characteristics of MM patients in Korea have not been fully investigated. Therefore, we aimed to understand the characteristics and management of Korean MM patients in a real-world setting by analyzing patients with high-risk cytogenetic abnormalities in the Korean Myeloma Registry. Methods: This is a retrospective observational study using the Korean Myeloma Registry, the web-based multicenter patient registry system established by the Korean Multiple Myeloma Working Party. Patients who are newly diagnosed with MM from 2010 to 2017 with at least one high-risk cytogenetic abnormality [t(4;14), t(14;16), or del(17p)] were included. Primarily, patients were classified by cytogenetic abnormality into three groups: Group 1, t(4;14) or t(14;16); Group 2, del(17p); and Group 3, t(4;14)/del(17p) or t(14;16)/del(17p). These patients were also stratified by the revised International Scoring System (R-ISS) and transplantation history for detailed analysis. We also used the number of cytogenetic abnormalities in an explanatory analysis; in this case, we included gain(1q). Progression-free survival (PFS) and overall survival (OS) were estimated, and the Hazard Ratio with the log-rank test was used for statistical comparison. Results: 391 out of 2170 MM patients from seven hospitals were identified as high-risk patients (men, 49.6%; median age, 63 years old). Median PFS for all patients was 18.9 months (95% CI 17.27-20.33), and the median OS was 44.6 months (95% CI 36.5-60.1). PFS (P OS was also significantly different between cytogenetic abnormality groups stratified by the revised International Staging System (R-ISS) (P=0.003). The lowest median OS durations were 16.9 months (95% CI 6.5-33.6) for del(17p) with R-ISS III, and 21.7 months (95% CI 9.3-N/A) for t(4;14)/del(17p) or t(14;16)/del(17p) with R-ISS III. Patients with higher R-ISS staging in the presence of del(17p) showed worse survival outcomes. Finally, PFS and OS were significantly inversely correlated with the number of cytogenetic abnormalities (P Conclusion: In real-world data from the Korean Myeloma Registry, we were able to observe the association of poor prognosis of MM patients with the number of cytogenetic abnormalities (PFS and OS) and R-ISS (OS). Moreover, we were also able to find the association of cytogenetic abnormality del(17p) and poor prognosis in MM patients. Lastly, we believe that this study provides the characteristics and management of MM patients needed to understand the real-world clinical course of high-risk MM patients in South Korea. Disclosures Kim: Amgen, BMS, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Yoon:Novartis: Consultancy, Honoraria; Janssen: Consultancy; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; YuhanPharma: Research Funding; Kyowahako Kirin: Research Funding; Amgen: Consultancy, Honoraria. Yoon:Celltrion: Honoraria; Samyang: Research Funding; Amgen, Chongkundang, Celgene, Astrazeneca: Consultancy. Lee:AMGEN: Current Employment.

Antihuman T-lymphocyte immune globulin (ATG) was shown to lower the incidence of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. The type, dose, and duration of ATG treatment is a matter of ongoing controversy in allo-HSCT. Furthermore, there has been no phase 3 study to explore the role of ATG-thymoglobulin for the prevention of cGVHD in allo-HSCT from matched siblings, whereas results from a recent randomized trial of ATG-Fresenius was reported (NEJM 2016). We performed a prospective, single-center, open-label, randomized trial of ATG-thymoglobulin as a part of the conditioning regimen. The primary endpoint was the cumulative incidence (CI) of cGVHD at a 2-year evaluation. A total of 126 patients with acute leukemia were planned to be enrolled and assigned randomly at a 1:1 ratio to receive ATG-thymoglobulin (1.25 mg/kg at three and two days before allo-HSCT) or receive no ATG-thymoglobulin stratified according to the refined Disease Risk Index and conditioning intensity. Both groups were well balanced for NCCN risk, disease type, disease status, and MRD status at HSCT. The current study finally enrolled 120 patients with a median of 560 days of follow-up (range 52 - 1257). The CI of cGVHD in the ATG group (n=60) and non-ATG (n=60) group at 2 years after allo-HSCT was 37.2% and 82.7%, respectively (p In conclusion, the current study revealed that the use of ATG-thymoglobulin, even at a relatively low dose (2.5 mg/kg), decreases the occurrence of cGVHD at a cost of an increased risk for relapse in the setting of allo-HSCT from matched sibling donors for acute leukemia. The optimal dose, timing, and duration of ATG-thymoglobulin should be investigated further. Disclosures Kim: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sun Pharma.: Research Funding; ILYANG: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AML Global Portal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL&H: Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy, Honoraria; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Yuhan: Consultancy, Honoraria; SL VaxiGen: Consultancy, Honoraria; AbbVie: Honoraria; Sanofi-Genzyme: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Purpose This study was performed to investigate the effect of exposure parameters on image quality obtained using a cone-beam computed tomography (CBCT) scanner and the relationship between physical factors and clinical image quality depending on the diagnostic task. Materials and methods CBCT images of a SedentexCT IQ phantom and a real skull phantom were obtained under different combinations of tube voltage and tube current (Alphard 3030 CBCT scanner, 78-90 kVp and 2-8 mA). The images obtained using a SedentexCT IQ phantom were analyzed technically, and the physical factors of image noise, contrast resolution, spatial resolution, and metal artifacts were measured. The images obtained using a real skull phantom were evaluated for each diagnostic task by 6 oral and maxillofacial radiologists, and each setting was classified as acceptable or unacceptable based on those evaluations. A statistical analysis of the relationships of exposure parameters and physical factors with observer scores was conducted. Results For periapical diagnosis and implant planning, the tube current of the acceptable images was significantly higher than that of the unacceptable images. Image noise, the contrast-to-noise ratio (CNR), the line pair chart on the Z axis, and modulation transfer function (MTF) values showed statistically significant differences between the acceptable and unacceptable image groups. The cut-off values obtained using receiver operating characteristic curves for CNR and MTF 10 were useful for determining acceptability. Conclusion Tube current had a major influence on clinical image quality. CNR and MTF 10 were useful physical factors that showed significantly associations with clinical image quality.

Table S2. Baseline characteristics of patients. (DOCX 22 kb)