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Simple Summary: We conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor in myeloma patients. Despite significantly less frequent (p = 0.045) use of plerixafor in the etoposide group, the optimal collection rates (CD34+ cells ≥ 6 × 106/kg) were not significantly different between the two groups (p = 0.195). In addition, the rate of collected CD34+ cells of ≥ 8.0 × 106/kg was significantly higher in the etoposide group. Our results suggest that single-dose etoposide plus G-CSF may be a better option for patients who are expected to receive two or more transplantations. To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 (p = 0.045). The median count of CD34+ cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; p = 0.018), but the optimal collection rate (CD34+ cells ≥ 6 × 106/kg) was not significantly different between the two groups (96.3% vs. 82.8%; p = 0.195). The rate of CD34+ cells collected of ≥ 8.0 × 106/kg was significantly higher in the etoposide group (77.8% vs. 44.8%; p = 0.025). Although the rates of grade II–IV thrombocytopenia (63.0% vs. 31.0%; p = 0.031) and grade I–IV nausea (14.8% vs. 0%; p = 0.048) were significantly higher in the etoposide group, the rates of adverse events were low in both groups, with no neutropenic fever or septic shock. Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations. [ABSTRACT FROM AUTHOR]

Background: Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. Objective: To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. Design: This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Methods: Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. Results: A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Conclusions: Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Plain language summary: Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies. [ABSTRACT FROM AUTHOR]

Vaccines are vital for public health, but concerns about adverse effects, particularly myocarditis and pericarditis linked to COVID-19 vaccines-, persist. This study investigates the application of Brighton Collaboration case definition to national vaccine safety data related to post-COVID-19 vaccine myo/pericarditis, utilizing claims under the Korea National Vaccine Injury Compensation Program (NIVCP). This study analyzed 190 medical records of individuals who claimed to have developed myo/pericarditis after receiving the COVID-19 vaccine, as reported to the NVICP between specified dates, categorizing cases based on the Brighton criteria for myocarditis or pericarditis. Between 2021–2022, NVICP received 190 cases meeting the Brighton criteria for myocarditis or pericarditis at levels 1, 2, or 3. Most cases fell into Level 2 (70%), followed by Level 1 (29%), and one at Level 3 (1%), with Level 1 cases showing a higher hospitalization rate (87.3%) and a notable proportion requiring admission to the Intensive Care Unit (25.5%). Chest pain and Troponin-I/T elevation were common findings in Level 1 cases, while Level 2 cases exhibited similar patterns but at a slightly lower frequency. Electrocardiogram and echocardiography findings differed between the two levels. The Brighton Collaboration case definition proved valuable for classifying and assessing AEFI data, enhancing our understanding of the potential relationship between myocarditis and the COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: The NIH protocol for non‐myeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low‐dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft‐versus‐host disease. However, alloSCT using NMA conditioning had been rarely applied to β‐thalassemia major (β‐TM) patients. Methods: To avoid prolonged immunosuppression, we developed a two‐stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH protocol. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immunosuppression or experiencing impending graft failure. Results: In this study, β‐TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four β‐TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion achieved complete (n = 4) or mixed chimerism (n = 1). The overall survival rate and event‐free survival at 4 years were 91.7% (95% CI; 53.9‐98.8) in both groups, with a thalassemia‐free survival rate in β‐TM patients of 87.5% (95% CI; 38.7‐98.1). Conclusion: This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult β‐TM patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Many post‐ERCP pancreatitis (PEP) risk factors, including pancreatic duct cannulation, have been identified; however, whether the number of repeated and unintentional wire placements (WPs) in the pancreatic duct during wire‐guided cannulation affects PEP risk is unknown. We aimed to identify the effects of repeated WP in the pancreatic duct and other potential risk factors on PEP incidence. Methods: We retrospectively analyzed 877 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). We examined potential patient‐related and procedure‐related risk factors, and PEP incidence by univariable and multivariable logistic regression analyses. Results: Thirty‐four patients (3.9%) had PEP. Univariable analysis revealed younger age, malignant common bile duct or ampulla of Vater stricture, two or more episodes of WPs in the pancreatic duct, and metal biliary stent as risk factors for PEP. Following multivariable analysis, two or more episodes of WPs in the pancreatic duct and metal biliary stent remained in the final model. PEP did not increase significantly in case of a one episode of WP (4.0%) compared with no episode of WP in the pancreatic duct (2.7%). However, patients with two episodes of WPs had 8.0% incidence and three or more episodes of WPs had 14.3%. Conclusions: A WP in the pancreatic duct and a metal biliary stent were associated with increased PEP incidence in patients undergoing ERCP. As for the pancreatic duct wire cannulation, two or more WPs considerably increased PEP incidence. This suggests that preventive measures or alternative procedures might be considered in patients with such cases during and after ERCP. [ABSTRACT FROM AUTHOR]

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 μg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 μg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 μg/g and 142.0 μg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 μg/g and 65.0 μg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease. [ABSTRACT FROM AUTHOR]

Purpose: There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms. Materials and Methods: We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36). Results: Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041). Conclusion: Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia. [ABSTRACT FROM AUTHOR]

Background & Aims Liver stiffness ( LS) value using transient elastography is a reliable, non-invasive tool for assessing liver fibrosis. LS-based prediction model, LSPS (=LS value × spleen diameter/platelet count) is well correlated with the risk of developing portal hypertension-related cirrhotic complications. Here, we assessed the prognostic performance of LSPS in predicting the development of hepatocellular carcinoma ( HCC) in patients with chronic hepatitis B ( CHB). Methods Between 2006 and 2010, we recruited 227 patients with CHB who underwent liver biopsy and LS measurement. The major end point was HCC development. Results Median age was 45 years and 156 (68.7%) patients were male. During the follow-up period (median, 61 months), HCC developed in 18 patients. Patient with HCC had a higher LS value, a longer spleen, and lower platelet counts (all P < 0.05) than those without HCC. On multivariate analysis, LSPS was identified as an independent predictor of HCC development [hazard ratio ( HR) 1.541, P < 0.001] after adjusting for age, serum albumin level and histological fibrosis stage. When patients were stratified into three groups (LSPS <1.1, 1.1-2.5 and >2.5), the 5-year cumulative risk of HCC increased significantly in association with a higher LSPS value (4.0, 13.8, 36.2%, respectively, P < 0.001). Patients with LSPS 1.1-2.5 ( HR 2.0, P = 0.032) and LSPS > 2.5 (HR 8.7, P = 0.002) had a higher risk of developing HCC than those with LSPS < 1.1. Conclusions LS value-spleen diameter to platelet ratio score is useful for assessing the risk of HCC development and careful surveillance strategies are required in an individual manner. [ABSTRACT FROM AUTHOR]

Even with the recent optimization of haploidentical stem cell transplantation (SCT), its role for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS (sAML) should be validated. We analyzed the outcomes of consecutive 60 patients with MDS or sAML who received T cell–replete haploidentical SCT after reduced-intensity conditioning with fludarabine, busulfan, and rabbit antithymocyte globuline ± 800 cGy total body irradiation. Patients achieved a rapid neutrophil engraftment after a median of 12 days (range, 8 to 23) and an early immune reconstitution without high incidences of acute graft-versus-host disease (GVHD) II to IV and chronic GVHD (36.7% and 48.3%, respectively). After a median follow-up of 4 years, incidence of relapse and nonrelapse mortality and rate of overall survival and disease-free survival was 34.8%, 23.3%, 46.8%, and 41.9%, respectively. In multivariate analysis, the disease status at peak was a significant predictor for relapse (lower-risk MDS versus higher-risk MDS or sAML; hazard ratio [HR], 5.69; 95% confidence interval [CI], 1.45 to 22.29; P = .013) and disease-free survival (HR, 4.44; 95% CI, 1.14 to 17.34; P = .032). Chronic GVHD was an additional significant predictor for relapse (no versus yes; HR, 2.87; 95% CI, 1.03 to 7.51; P = .043). Our T cell–replete haploidentical SCT may be a feasible option for patients with MDS and sAML without conventional donors. [ABSTRACT FROM AUTHOR]

Background In unrelated donor allogeneic stem cell transplantation ( URD- SCT), most studies reported that peripheral blood stem cells ( PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease ( GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD- SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin®, 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM. Methods To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD- SCT with PBSC ( n = 70) or BM ( n = 45) using our risk-adapted GVHD prophylaxis strategy. Results The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different. Conclusion Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD- SCT. [ABSTRACT FROM AUTHOR]

Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG ( n = 46) or rabbit ATG ( n = 53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % ( P = 0.421), 39.1 versus 45.3 % ( P = 0.537), 45.7 versus 49.1 % ( P = 0.735), and 47.8 versus 50.9 % ( P = 0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P = 0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % ( P = 0.387) at 12 months and 21.7 versus 22.6 % ( P = 0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival ( P = 0.460) and failure-free survival ( P = 0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion. [ABSTRACT FROM AUTHOR]

For the first time, we have fabricated a novel Switchable Transmissive and Reflective (STR) LCD based on dual gap TN (Twisted-Nematic) mode using a general a-Si TFT process. This new technology creates ultra low power LCD using reflective mode. This new device has no power consumption of backlight in ordinary room light environment. Moreover our new LCD offers superior outdoor visibility and enhanced portability to user. We will show vision as a future LCD mode for portable electronic devices. [ABSTRACT FROM PUBLISHER]

Homogeneously aligned nematic liquid crystal (LC) cells doped with carbon nanotubes (CNTs) driven by an in-plane field were fabricated and their electro-optic characteristics were investigated. The effective cell retardation values showed no difference between doped and undoped LC cells in the absence of electric field. However, in the presence of electric field, it was smaller in the CNT-doped cell than in the undoped cell, resulting in the decrease of transmittance. Furthermore, the CNT-doped cell exhibited a slight increase in the driving voltage due to the increase of the twist elastic constant (K22) and the decrease in the decay response time due to the decrease in the rotational viscosity (γ) and γ/K22 compared to the undoped cell. [ABSTRACT FROM AUTHOR]

Introduction: Carfilzomib plus dexamethasone (Kd) is widely used in patients with relapsed and/or refractory multiple myeloma (RRMM). However, the treatment outcomes of Kd, especially in trial-unfit patients, have not been extensively studied in the real-world setting. Methods: We analyzed the outcomes of 152 RRMM patients who received Kd at our hospitals from April 2018 to March 2022. Results: At the commencement of Kd, patients received a median of two (range 1–7) lines of prior anti-myeloma therapy. According to the ENDEAVOR study criteria, 93 (61.2%) and 59 (38.8%) patients were classified as the trial-fit and the trial-unfit group, respectively. The overall response (OR) rate for the entire cohort was 71.1% (95% CI 63.2–78.1%). Progression-free survival (PFS) and overall survival (OS) were 5.6 months (95% CI 3.9–6.9 months) and 24.0 months (95% CI 13.4–38.0 months), respectively. There was no significant difference in the OR rate between the trial-fit and the trial-unfit groups (76.3% vs. 62.7%; P = 0.105). However, the median PFS (3.6 months vs. 7.3 months; P < 0.001) and OS (15.0 vs. 36.8 months; P = 0.009) were significantly shorter in the trial-unfit group. On multivariate analysis, trial-fitness (unfit vs. fit) remained a significant covariate influencing the TRM (HR: 4.84, 95% CI 1.66–14.06; P = 0.004) and PFS (HR: 1.82, 95% CI 1.27–2.62; P = 0.001). Conclusion: Our data suggest that the treatment outcomes of Kd are acceptable in the real-world setting with significant differences between the trial-fit and the trial-unfit groups, although they are relatively inferior to those of a pivotal trial. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the surgical outcomes of arthroscopic pull-out repair for medial meniscus root tear (MMRT) combined with the marrow stimulation procedures (MSP) for accompanying high-grade cartilage lesions. Methods: Patients who underwent arthroscopic pull-out repair for MMRT between 2010 and 2019 were retrospectively reviewed. Patients who had at least 3 years of follow-up were included and classified into two groups according to whether MSP (microfracture or microdrilling) were performed on cartilage lesions in the medial tibiofemoral joint (group 1, patients with International Cartilage Repair Society [ICRS] grade 0–3a lesions and did not undergo MSP; group 2, patients with ICRS grade 3b–3d lesions and underwent MSP). Comparative analyses, including non-inferiority trials, were conducted between groups for subjective and objective outcomes. In addition, group 2 was further divided into two subgroups according to cartilage lesion size and compared with group 1 (group S, ≤ 2.0 cm2; group L, > 2.0 cm2). Results: A total of 94 patients were included (group 1, 68 patients; group 2, 26 patients). There were no significant differences in clinical scores at postoperative 3 years and final follow-up between groups 1 and 2, but group 2 failed to satisfy the non-inferiority criteria compared to group 1 overall. In objective outcomes, group 2 did not meet the non-inferiority criteria for the rate of osteoarthritis progression compared to group 1, and it also showed a significantly higher proportion of high-grade osteoarthritis at final follow-up (P = 0.044) and a higher degree of osteoarthritis progression than group 1 (P = 0.03 for pre- to postoperative 3 years, and P = 0.006 for pre- to final follow-up). In additional evaluations comparing the subgroups of group 2 and group 1, group S showed relatively favourable results compared to group L in objective outcomes at final follow-up. Conclusion: Patients who underwent arthroscopic pull-out repair for MMRT combined with MSP for accompanying high-grade cartilage lesions showed suboptimal outcomes compared to those with no or low-grade lesions at mid-term follow-up. High-grade cartilage lesions ≤ 2.0 cm2 may be candidates for the surgical repair of MMRT if MSP are performed, but those with larger lesions may require alternative treatment strategies. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Background: Bortezomib-melphalan-prednisone (VMP) and lenalidomide-dexamethasone (Rd) remain the standard treatments for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). This study aimed to compare real-world benefits between the two regimens. We also were interested in exploring efficacy according to subsequent therapy following VMP or Rd. Methods: A total of 559 NDMM patients treated with VMP (n = 443, 79.2%) or Rd (n = 116, 20.8%) was recruited retrospectively from a multicenter database. Results: Rd provided more benefits than VMP—overall response rate: 92.2 vs. 81.8%, p = 0.018; median progression-free survival (PFS): 20.0 vs. 14.5 months, p <0.001; second PFS (PFS2): 43.9 vs. 36.9 months, p = 0.012; overall survival (OS): 100.1 vs. 85.0 months, p = 0.017. Multivariable analysis revealed significant benefits of Rd over VMP, with hazard ratios of 0.722, 0.627, and 0.586 for PFS, PFS2, and OS, respectively. In propensity score-matched cohorts with matched VMP (n = 201) and Rd (n = 67) arms to balance baseline characteristics, Rd still showed significantly better outcomes for PFS, PFS2, and OS than VMP. Following VMP failure, triplet therapy showed significant benefits for response and PFS2; after Rd failure, PFS2 with carfilzomib-dexamethasone was significantly better than bortezomib-based doublet treatment. Conclusion: These real-world findings may assist with better selection between VMP and Rd as well as subsequent therapy for NDMM. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the outcomes of conservative treatment for recurrent shoulder dislocation without subjective apprehension, despite the presence of a Bankart lesion or glenoid defect. Methods: A retrospective analysis was performed for 92 patients with recurrent shoulder dislocation treated with conservative treatment due to negative apprehension between 2009 and 2018. The failure of the conservative treatment was defined as a dislocation or subluxation episode or subjective feeling of instability based on a positive apprehension. The Kaplan–Meier method was used to estimate failure rates over time, and a receiver operating characteristic (ROC) curve was constructed to determine a cut-off value for a glenoid defect. The clinical outcomes were compared between patients who completed conservative treatment without recurrence of instability (Group A) and those who failed and subsequently underwent surgical treatment (Group B) using shoulder functional scores and sports/recreation activity level. Results: This retrospective study included 61 of 92 eligible patients with recurrent shoulder dislocation. Among the 61 patients, conservative treatment failed in 46 (75.4%) over the 2-year study period. The cut-off value for a glenoid defect was 14.4%. The association between glenoid defect size (≥ 14.4% or as a continuous variable) and survival was statistically significant (p = 0.039 and p < 0.001, respectively). The mean glenoid defect size in Group B increased from 14.6 ± 3.0% to 17.3 ± 3.1% (p < 0.001), and clinical outcomes for Group A were inferior to those for Group B at the 24-month follow-up. Conclusions: Conservative treatment for recurrent shoulder dislocation in patients without subjective apprehension showed a high failure rate during the study period, especially if the glenoid defect was ≥ 14.4% in size. Despite clinical improvement in patients who completed conservative treatment without recurrence, functional outcome scores and sport/recreation activity levels were better in the patients who underwent arthroscopic Bankart repair. Therefore, for recurrent anterior shoulder instability, even without subjective apprehension, surgical treatment is warranted over conservative treatment. Level of evidence: Level IV. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of the response to induction therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171 patients who were newly diagnosed with MM and underwent early ASCT were analyzed. One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA-based induction therapy. After a median follow-up of 45.4 months, the 4-year overall survival (OS) and progression-free survival (PFS) from transplantation were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and 15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses revealed that the patients who had NA-based induction had a significantly shorter OS ( P < 0.001) and PFS ( P < 0.001) when at least a partial response (PR) was not achieved. In patients who did not receive NAs before ASCT, lack of at least a PR to induction therapy was not associated with a survival disadvantage. These findings suggest that, unlike pretransplantation induction before NAs, patients who do not respond to induction treatment using NAs may not derive a benefit from ASCT. The relevance of induction failure differs for corticosteroid- and NA-based induction. [ABSTRACT FROM AUTHOR]

The major limitation of autologous stem cell transplantation (auto- SCT) in non- Hodgkin lymphoma ( NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto- SCT at complete ( n = 41) or partial remission ( n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34+ cells using a Clini MACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto- SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group ( n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34+ purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34+ purification in auto- SCT for NHL. [ABSTRACT FROM AUTHOR]

Data for 125 patients with cytogenetically normal acute myeloid leukemia (CN-AML) regarding BAALC and combinatorial molecular markers at diagnosis were evaluated. Fewer patients with higher BAALC expression at diagnosis achieved a complete remission (CR) (49.2 vs. 75.8%, p = 0.002) after the first cycle of chemotherapy, and there were more primary refractory cases (37.3 vs. 18.2%, p = 0.017). In a combinatorial analysis, FLT3-ITD-positive patients with higher BAALC showed more refractoriness and the worst overall survival (OS) ( p < 0.001) and disease-free survival (DFS) ( p < 0.001) in CN-AML. When NPM1-mutated CN-AML was combined with either FLT3-ITD mutation or higher BAALC expression, both OS ( p = 0.043) and DFS ( p = 0.008) were worse; when combined with both, it showed the worst OS ( p < 0.001) and DFS ( p = 0.004). Higher BAALC expression and FLT3-ITD mutation, both individually and in combination, were associated with worse survival outcomes in CN-AML, and this was also applicable in NPM1-mutated CN-AML, known as a favorable-risk group. [ABSTRACT FROM AUTHOR]

Abstract: Karyotype is a powerful prognostic factor for complete remission (CR) and overall survival (OS) in acute myelogenous leukemia (AML). Adverse-risk karyotype AML is now treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) to overcome relapse. We attempted to stratify patients with this disease using a combination of known factors. We evaluated clinical correlates in 211 adults with AML and adverse-risk karyotypes. We divided the patients into several subgroups based on the number of chromosomal aberrations (NCAs), normal karyotype (NK) mosaicism, and monosomal karyotype (MK) status. CR rates and survival outcomes were compared among the subgroups, and the relapse rate was calculated in the allo-HSCT subgroup. The cutoff of NCA ≥5 showed the worst OS (P < .001) compared with NCA ≥3 or NCA ≥4 even after allo-HSCT. NK mosaicism significantly improved OS in both the NCA <5 (P = .024) and NCA ≥5 (P = .030) subgroups, but after allo-HSCT, it showed a favorable effect only in the NCA <5 subgroup. MK showed worse OS (P = .041), but there was no significantly worse effect after allo-HSCT compared with non-MK. Finally, we stratified patients into 4 subgroups, NCA ≥5 and NCA <5 with and without NK mosaicism. The most favorable OS and lower relapse rate after allo-HSCT were achieved by the NCA <5 with NK mosaicism subgroup, and the NCA ≥5 without NK mosaicism subgroup showed the worst prognosis in both entire group and allo-HSCT subgroup analysis. This study reveals that the combination of NCA and NK mosaicism may predict survival outcomes accurately, and suggests that novel treatment strategies for highly adverse-risk group AML should be tailored in the future. [Copyright &y& Elsevier]

No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML ( CBF- AML) from diagnosis to hematopoietic stem cell transplantation ( HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction ( RQ- PCR) at diagnosis, after induction chemotherapy, at pre- HSCT, and at post- HSCT period in 45 consecutive patients [t(8,21) ( n = 28), inv(16) (n = 17)], who received HSCT as a post-remission treatment. BAALC and WT1 RQ- PCR decrement ratio ( DR) was also calculated at post-induction chemotherapy, at pre- HSCT, and at post- HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS ( P = 0.031), EFS ( P = 0.011), and higher CIR ( P = 0.002) rates. At post- HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS ( P = 0.005, 0.016), EFS ( P = 0.002, 0.006), and higher CIR ( P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post- HSCT were also associated with inferior OS ( P = 0.018, 0.015) and higher CIR rates ( P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post- HSCT showed significantly lower CIR rate ( P = 0.028). This study showed that higher post- HSCT BAALC and WT1 expressions in patients with CBF- AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. [ABSTRACT FROM AUTHOR]

Background: Endoscopic snare papillectomy (ESP) has been established as a safe and effective treatment for ampullary adenomas. However, little is known about the optimal post-procedure follow-up period and the role of routine endoscopic surveillance biopsy following ESP. We aimed to evaluate patient adherence to a 5-year endoscopic surveillance and routine biopsy protocol after ESP of ampullary adenoma. Methods: We reviewed our prospectively collected database (n = 98), all members of which underwent ESP for ampullary lesions from January 2011 to December 2016, for the evaluation of long-term outcomes. The primary outcome was the rate of patient adherence to 5-year endoscopic surveillance following ESP. The secondary outcomes were the diagnostic yield of routine endoscopic biopsy, recurrence rate, and adverse events after endoscopic surveillance in the 5-year follow-up (3-month, 6-month, and every 1 year). Results: A total of 19 patients (19.4%) experienced recurrence during follow-up, all of these patients experienced recurrence within 3 years of the procedure (median 217 days, range 69–1083). The adherence rate for patients with sporadic ampullary adenoma were 100%, 93.5%, and 33.6% at 1, 3, and 5 years after ESP, respectively. The diagnostic yield of routine endoscopic biopsy without macroscopic abnormality was 0.54%. Pancreatitis occurred in four patients (4%, 3 mild, 1 moderate) after surveillance endoscopic biopsy without macroscopic abnormality. Conclusions: Given the low 5-year adherence rate and diagnostic yield of routine endoscopic biopsy with risk of pancreatitis, optimal surveillance intervals according to risk stratification (low grade vs. high grade adenoma/intramucosal adenocarcinoma) may be required to improve patient adherence, and routine biopsy without macroscopic abnormality may not be recommended. [ABSTRACT FROM AUTHOR]

Abstract: Using real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD–negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD–negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT. [Copyright &y& Elsevier]

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome ( MDS) according to their response to hypomethylating agents ( HMA). While 2-yr disease-free survival ( DFS) of patients who transformed to acute myeloid leukemia ( n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G- COR (group of continuous response, n = 19), G- No C (group of no change, n = 15), G- LOR (group of loss of response, n = 6), and G- DP (group of disease progression, n = 4), respectively. When dichotomized as G- COR/ G- No C versus G- LOR/ G- DP, significantly different 2-yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G- LOR/ G- DP [hazard ratio ( HR), 3.91; P = 0.008] and poor karyotype at transplantation ( HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G- LOR/ G- DP was for relapse ( HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher-risk MDS ( Hr MDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G- COR showed a trend of better DFS compared with G- No C among Hr MDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation ( HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for Hr MDS. [ABSTRACT FROM AUTHOR]

To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed. [Copyright &y& Elsevier]

Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 patients with acute myeloid leukemia (AML) who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate- or poor-risk disease by National Comprehensive Cancer Network guidelines (2017, version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; busulfan plus cyclophosphamide or cyclophosphamide plus total body irradiation) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms tumor gene 1 (WT1) expression results before transplant. We and other groups serially published a predictive value for pretransplant WT1 expression in patients with AML to identify patients at higher risk of relapse. Among the total 257 patients, 191 (74.3%) and 66 (25.7%) patients received MAC and RIC transplants, respectively. WT1 ≥250 copies/104 ABL was defined as WT1high. WT1high before SCT was found to be an independent prognostic factor for inferior overall survival (OS), disease-free survival (DFS), and higher cumulative incidence of relapse (CIR). There were 201 patients with WT1 low expression based upon pretransplant analysis. There was no significant difference in OS, DFS, CIR, and nonrelapse mortality between MAC and RIC patients. To conclude, post-transplant survival or relapse was not different by conditioning intensity in AML CR1 patients whose WT1 level was below 250 copies per 104 ABL at transplantation. [ABSTRACT FROM AUTHOR]

• A regimen of fractionated total body irradiation 600 cGy/fludarabine/intermediate-dose antithymocyte globulin (5 mg/kg) results in feasible outcomes. • Donor type and comorbidities affected graft-versus-host disease–free and failure-free survival. • Upfront application of haploidentical stem cell transplantation in patients with very severe aplastic anemia might be suggested. The aim of this study was to verify the feasibility of rabbit antithymocyte globulin (ATG; 5 mg/kg) in combination with 600 cGy of fractionated total body irradiation (fTBI; 3 doses of 200 cGy) and fludarabine (Flu; 150 mg/m2) as a conditioning regimen for haploidentical stem cell transplantation from a related mismatched donor (haplo-SCT) in adult patients with severe aplastic anemia (SAA). We analyzed 47 consecutive patients who underwent haplo-SCT, including 24 patients from our previous pilot report. The median age was 36.0 years (range, 17 to 61 years), and 25 patients (53%) were very severe aplastic anemia (VSAA) at transplantation. All patients achieved primary engraftment. The cumulative incidence of grade ≥II acute graft-versus-host disease (GVHD) and chronic moderate or greater GVHD was 27.7% at 100 days and 13.5% at 3 years, respectively. With a median follow-up of 32.3 months, the 3-year probability of overall survival and failure-free survival was 91.0% and 88.6%, respectively. The 3-year GVHD- and failure-free survival (GFFS) was 71.6%. Offspring donor and lower comorbidity index were independent factors correlated with higher GFFS in multivariate analysis. In conclusion, the outcomes of haplo-SCT with fTBI 600 cGy/Flu/ATG-5 indicate that haplo-SCT can be an effective alternative option when a fully matched donor is not available or a patient with VSAA needs an urgent transplantation. [ABSTRACT FROM AUTHOR]

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 <.0001) were compared. Results: Median time to engraftment was similar. Two‐year cumulative incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) was significantly lower in the ATG group (15% vs 55%, P <.0001), while that of acute GVHD was similar compared with the no‐ATG group. After a median follow‐up of 60 months (range, 14‐184), the 3‐year cumulative incidences of non‐relapse mortality and relapse were 9% and 21% for ATG group and 15% and 19% for no‐ATG group (P =.408 and P =.717), respectively, leading to a significantly better 3‐year GVHD‐free and relapse‐free survival (GRFS) in the ATG group (55% vs 19%, P =.006): The 3‐year overall and disease‐free survival were similar. Infectious complication occurred with similar frequencies in both groups. Conclusion: These findings suggest that ATG can be safely used to decrease moderate‐to‐severe chronic GVHD with improved GRFS for patients with MDS receiving MSD‐HSCT in RIC setting. [ABSTRACT FROM AUTHOR]

• WT1 assay is useful for predicting post-transplant relapse in acute myeloid leukemia (AML). • Optimal threshold for the WT1 assay would be 250 copies/104 copies of ABL1. • WT1 assay is particularly available in AML without specific molecular targets. • WT1 assay in each risk group by time points have different significance. 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. [ABSTRACT FROM AUTHOR]

Highlights • The 3-year GVHD-free, relapse-free survival rate for myelodysplastic syndrome was 34.5%. • Circulating blast, cytogenetics, HCT-CI, MAC/RIC, and ATG dose were factors predicting GRFS. • Risk-stratified GRFS rates were 64.9% in low-risk, 33.6% in intermediate-risk, and 6.6% in high-risk patients. • There was an evident impact of RIC and ATG ≥ 7. 5mg/kg on low-risk patients by the other 3 factors. • There was no evident impact of RIC and ATG ≥ 7.5 mg/kg on high-risk patients by the other 3 factors. Graphical Abstract Image, graphical abstract Abstract Graft-versus-host disease–free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan–based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [<7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6% in intermediate risk, and 6.6% in high risk; P <.001) were identified. Fixed factor–adjusted GRFS in patients receiving reduced-intensity conditioning (RIC) plus high-dose ATG (≥7.5 mg/kg) was superior (P <.001) to those receiving MAC and/or low-dose ATG. Favorable influences of RIC plus ATG ≥ 7.5 mg/kg were evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus 4.4%; P <. 001) but were not evident in the high-risk group (3-year GRFS,.0% versus 5.3%; P =.678). Conclusively, this study suggests that risk-adapted selection of conditioning intensity and ATG could improve qualified HSCT outcomes. [ABSTRACT FROM AUTHOR]

Objective: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), andLens culinarisagglutinin-reactive fraction of AFP (AFP-L3).Material and methods: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence.Results: Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728–0.801) for AFP; 0.823 (95% CI, 0.791–0.854) for PIVKA-II; and 0.755 (95% CI, 0.718–0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691–0.816) for AFP, 0.701 (95% CI, 0.630–0.771) for PIVKA-II, and 0.670 (95% CI, 0.596–0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851–0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704–0.841) for early HCC diagnosis.Conclusion: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients. [ABSTRACT FROM PUBLISHER]

This study explored the influence of mismatched inhibitory killer cell immunoglobulin–like receptor (KIR) ligands on the outcome of haploidentical transplantation using T cell–replete, granulocyte colony–stimulating factor–mobilized peripheral blood stem cells in adult patients with acute myeloid leukemia (AML). Three groups were examined: unidirectional graft-versus-host KIR ligand mismatched (GVH-KIR-MM; n = 33), bidirectional KIR ligand matched (KIR-M; n = 41), and unidirectional host-versus-graft KIR ligand mismatched (HVG-KIR-MM; n = 26). All recipients were treated with the same conditioning regimen (800 cGy total body irradiation, fludarabine, busulfan, and antithymocyte globulin). After a median follow-up of 26 months, the 2-year cumulative incidence of relapse was significantly higher in HVG-KIR-MM (40.3% ± 10.3%) versus others (18.9% ± 4.8%, P = .044). In the standard-risk group, the 2-year disease-free survival (DFS) was significantly lower in HVG-KIR-MM (51.8% ± 11.2%) compared with GVH-KIR-MM (88% ± 8.1%, P = .025). Multivariate analysis showed that HVG-KIR-MM was significantly associated with higher relapse (hazard ratio [HR], 10.7; P = .002) and lower DFS (HR, 3.4; P = .012). Subgroup analysis revealed increased DFS with higher doses of CD3 + CD8 + and CD3 - CD56 + grafts in GVH-KIR-MM (90.9% ± 8.7%, P = .006); there was no such effect in the other groups. Although our conclusions are limited by the absence of donor KIR genotype data, our study suggests unidirectional KIR ligand incompatibility in the host-versus-graft vector has a detrimental effect on T cell–replete haploidentical transplantation outcomes in adult patients with AML. [ABSTRACT FROM AUTHOR]

We analyzed the outcome of stem cell transplantation (SCT) for 59 acute myeloid leukemia (AML) patients with t(8;21). The 5-year overall and disease-free survival (OS and DFS) were 70.2 and 68.4%, respectively. The 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality were 16.9 and 13.6%, respectively. OS and DFS in the reduced-intensity conditioning (RIC)-SCT group (70.4%) were not different from in the autologous SCT (ASCT) group (72.4 and 69.0%, respectively). Age was a factor affecting OS (p = 0.007) and DFS (p = 0.008) in the ASCT group, but not in the RIC-SCT group. In the ASCT group, lack of the X chromosome (-X) and an age of >50 years were associated with inferior survival; however, these differences disappeared in the RIC-SCT group. CIR was significantly higher in patients with -X than in those without -X only in the ASCT group (p = 0.038), i.e. not in the RIC-SCT group. ASCT and RIC-SCT are equally effective for the intensification of postremission treatment of AML patients with t(8;21). The subgroups with advanced age or -X should be preferentially considered for RIC-SCT, rather than ASCT. Further investigations with randomized prospective trials of a sizeable study population are warranted. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The prognostic impact of extramedullary plasmacytomas (EMPs) on newly diagnosed symptomatic multiple myeloma (MM) was evaluated in the context of treatment approach including autologous stem cell transplantation (ASCT) and chemotherapy alone. A total of 275 consecutive patients with newly diagnosed MM were included, and 54 patients (19.6 %) had EMPs at diagnosis. Patients with initial EMPs were more likely to have myeloma bone disease but favorable laboratory parameters in hemoglobin and β2-microglobulin. Patients were treated with different schemas based on transplant eligibility (154 in ASCT-eligible vs. 121 in ASCT-ineligible). After a median follow-up of 24.6 months (range, 0.2-56.3 months) in survivors, patients with initial EMPs had significantly worse progression-free survival (PFS) ( P = 0.035) and overall survival (OS) ( P = 0.006) compared to those without initial EMPs. In the multivariate analyses, the presence of initial EMPs was an independent prognostic factor for PFS (relative risk (RR) of 2.24, P = 0.024) and OS (RR of 2.47, P = 0.027) in the transplant-ineligible patients, whereas it did not significantly influence PFS ( P = 0.341) or OS ( P = 0.499) in the transplant-eligible patients. However, the adverse impact of EMPs observed in transplant-ineligible patients was attenuated among the patients treated with bortezomib. These data suggest that ASCT can overcome the negative impact of EMPs and highlight the potential efficacy of bortezomib on EMPs in the non-transplant setting. [ABSTRACT FROM AUTHOR]

CD161 is a type II transmembrane glycoprotein with characteristics of the C-type lectin superfamily, which has recently been shown to promote T cell expansion. In this study, the role of T cells expressing CD161 as a predictor for the occurrence of acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation (SCT) was investigated. Sixty-one patients who underwent first allogeneic SCT were enrolled. At engraftment, the expression of CD3, CD4, CD8, CD161, CD16, and CD56 was analyzed by flow cytometry. After adjusting for potential variables by univariate analysis, we performed a multivariate analysis, which revealed a low frequency of CD8 + CD161 + cells ( P = .034) and a high ratio of CD4 + CD161 + to CD8 + CD161 + cells ( P = .001) were associated with the occurrence of aGVHD with a grade of ≥ II. Moreover, the frequency of CD8 + CD161 + T cells was negatively correlated with aGVHD grade. A separate analysis for visceral aGVHD showed similar results, with a low frequency of CD8 + CD161 + T cells ( P = .031) or a high ratio of CD4 + CD161 + to CD8 + CD161 + cells ( P < .001), indicating a high risk. Also, the predictive role of serum IL-17 levels for the occurrence of aGVHD was identified, and RORγT was more highly expressed in CD4 + CD161 + T cells than in CD8 + CD161 + T cells after allogeneic SCT ( P = .032). Although our study was limited by the heterogeneity and small number of patients, these results suggest that the CD8 + subset of CD161 + T cells may have regulatory effects and that they provide a basis for predicting the occurrence of aGVHD after allogeneic SCT. [ABSTRACT FROM AUTHOR]

Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern in myelodysplastic syndromes (MDS), but the role of Wilms tumor gene 1 ( WT1 ) as a predictive marker for post-HSCT relapse remains to be validated. We measured WT1 transcript levels by real-time quantitative PCR from marrow samples of 82 MDS patients who underwent transplantation between 2009 and 2013. Pre-HSCT WT1 expression weakly correlated with marrow blast counts or International Prognostic Scoring System scores and failed to predict post-transplantation relapse. Regarding post-HSCT WT1 , transcript levels of relapsed patients were significantly higher in comparison to those in remission. Further analysis using receiver operating characteristics curves showed that higher (>154 copies/10 4 ABL ) 1-month post-HSCT WT1 resulted in a higher 3-year relapse rate (47.2% versus 6.9%, P < .001) with poorer disease-free survival (DFS) and overall survival at 3 years (41.7% versus 79.0% and 54.3% versus 82.1%, P = .003 and P = .033, respectively). Multivariate analysis after adjusting for pre-HSCT karyotype and chronic graft-versus-host disease (GVHD) also revealed that higher 1-month post-HSCT WT1 was an independent predictive marker for subsequent relapse ( P = .002) and poorer DFS ( P = .010). In the higher 1-month post-HSCT WT1 subgroup, patients with chronic GVHD showed lower relapse rate and favorable survival outcome. One month post-HSCT WT1 expression was a useful marker for minimal residual disease and relapse prediction in association with chronic GVHD in the context of HSCT for MDS. [ABSTRACT FROM AUTHOR]

Background & Aims Liver stiffness ( LS) measurement using transient elastography and the FibroTest ( FT) are alternatives to liver biopsy ( LB) in assessing liver fibrosis. We investigated the prognostic role of the combined use of LS and FT in predicting liver-related events ( LREs) in patients with chronic hepatitis B ( CHB). Methods Consecutive patients with CHB who underwent LB, along with LS and FT on the same day were recruited. LRE was defined as hepatic decompensation, hepatocellular carcinoma ( HCC) or liver-related death. Results A total of 151 patients (86 male) were analyzed. During follow-up (median 59.9 months), overall 18 (11.9%) patients experienced LREs. The areas under receiver-operating characteristic curves of LS, FT, LS + FT and LS × FT in predicting LRE were 0.701, 0.668, 0.702 and 0.741 respectively. After adjusting for age and histological fibrosis staging, significant variables in univariate analysis (both P < 0.05), LS + FT and LS × FT were independent predictors of LREs with hazard ratios ( HRs) of 1.080 and 1.126 (all P < 0.05) respectively. When subjects were divided into three groups according to quartile stratification (low quartile, interquartile and high quartile) using LS + FT and LS × FT, cumulative LRE development rate significantly increased with a corresponding increase in value among three groups respectively (log-rank test, all P < 0.05). Conclusion The combined use of LS and FT significantly predicted forthcoming LRE development, but with only a slight additional benefit compared to LS or FT alone. [ABSTRACT FROM AUTHOR]

Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell–replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m 2 /day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days −4 to −1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8 + and CD4 + T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR. [ABSTRACT FROM AUTHOR]

Background and Aims Chronic hepatitis B ( CHB) can progress to cirrhosis, hepatocellular carcinoma ( HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side-effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. Methods Between 2001 and 2005, treatment-naïve Korean CHB patients without cirrhosis were enrolled and followed up for at least 5 years. During follow up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary end-points were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. Results Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [ HR] 1.075, 95% confidence interval [ CI] 1.037-1.116; P < 0.001), whereas age ( HR 1.060, 95% CI 1.012-1.111; P = 0.014) and cirrhosis ( HR 17.470, 95% CI 5.081-60.063; P < 0.001) were those for developing HCC. Conclusions In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance. [ABSTRACT FROM AUTHOR]

Objectives For patients with acute myeloid leukemia in first complete remission ( AML CR1) lacking HLA-matched sibling donors ( MSD), 8/8-matched unrelated donors ( URD) are mostly used in cases with poor-risk features. For AML CR1 with intermediate cytogenetics, however, the benefit of 8/8-matched URD should be compared with non-allogeneic therapies as well as MSD. Methods To address this issue, we assessed the transplantation outcomes of 8/8-matched URD ( n = 54) compared with MSD ( n = 145) or autologous transplantation ( n = 89) for AML CR1 with intermediate cytogenetics. Results In multivariate analyses, 8/8-matched URD had comparable 6-yr overall survival (OS, P = 0.997), disease-free survival ( DFS, P = 0.951), and relapse ( P = 0.672) to MSD, whereas 8/8-matched URD had a higher OS ( P = 0.070) and DFS ( P = 0.035) with lower relapse ( P = 0.009) than autologous transplantation. No difference in non-relapse mortality was observed according to donor type. Notably, these equivalent or superior outcomes of 8/8-matched URD compared with MSD or autologous transplantation, respectively, were particularly evident in patients without poor-risk features ( n = 200), such as older age, hyperleukocytosis at diagnosis, and myelodysplasia-related changes, who are not usual candidates for URD transplantation. Conclusions These results indicate that 8/8-matched URD are feasible next option in AML CR1 with intermediate cytogenetics, when lacking MSD, even in patients without poor-risk features. [ABSTRACT FROM AUTHOR]

Cytomegalovirus gastrointestinal (CMV-GI) disease in GI graft-versus-host disease (GI-GVHD) has not been properly evaluated in the era of preemptive therapy for CMV infection. We investigated 103 patients with GI-GVHD who underwent endoscopic biopsies with immunohistochemical staining for CMV. All recipients and/or donors were seropositive for CMV and monitored with a strategy of preemptive therapy based on real-time quantitative polymerase chain reaction. Twenty-six patients (25 %) developed CMV-GI disease, especially in HLA-mismatched transplants ( P = 0.023) and with initial gut involvement of GVHD ( P = 0.009). The CMV-GI diseases were diagnosed at follow-up endoscopies ( n = 10, 39 %), comprising 19 % of 52 patients who underwent follow-up endoscopies, as well as initial endoscopies ( n = 16, 61 %), comprising 16 % of all GI-GVHD patients. In seven cases, either at initial ( n = 5) or follow-up endoscopies ( n = 2), CMV-GI disease was diagnosed in the absence of histopathologic evidence for GI-GVHD. Notably, only 11 patients (42 %) had prior CMV DNAemia before the diagnosis of CMV-GI disease, while 12 (46 %) and three (12 %) had concurrent and no CMV DNAemia, respectively. Sixty-five percent of CMV-GI disease was resolved by additional antiviral therapies, but CMV-GI disease ( P = 0.032) as well as severity of GVHD ( P = 0.001) negatively affected GVHD-specific survival. In conclusion, our data demonstrate that CMV-GI disease was a cause of initial or persistent GI manifestations after the initiation of therapy in a considerable proportion of GI-GVHD. These suggest the necessity of novel strategies to reduce CMV-GI disease as well as an effort to confirm CMV with repeated endoscopies. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute myeloid leukemia (AML) with RUNX1-RUNX1T1 is a heterogeneous disease entailing different prognoses. Patients with high-risk features can benefit from allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT. However, insufficient data about major risk factors, such as KIT mutations and measurable residual disease (MRD) status for relapse, make it difficult to clarify the benefit of each transplant strategy. Moreover, limited data are available to elucidate the exact prognostic impacts of different types of KIT mutations and optimal thresholds or time points for RUNX1–RUNX1T1 MRD assessment, particularly in the setting of HSCT. Given the lack of prospective study, the current retrospective study, including a large cohort of high-risk AML patients with RUNX1–RUNX1T1, firstly demonstrated the differentiated prognostic impact of D816V KIT mutation among various KIT mutations and clarified optimal time points and thresholds for RUNX1–RUNX1T1 MRD monitoring in the setting of HSCT. The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches. [ABSTRACT FROM AUTHOR]