Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML.

Given that there are only a few prospective studies with conflicting results, we investigated the prognostic value of multiparameter geriatric assessment (GA) domains on tolerance and outcomes after intensive chemotherapy in older adults with acute myeloid leukemia (AML). In all, 105 newly diagnosed patients with AML who were older than age 60 years and who received intensive chemotherapy consisting of cytarabine and idarubicin were enrolled prospectively. Pretreatment GA included evaluations for social and nutritional support, cognition, depression, distress, and physical function. The median age was 64 years (range, 60-75 years), and 93% had an Eastern Cooperative Oncology Group performance score <2. Between 32.4% and 69.5% of patients met the criteria for impairment for each domain of GA. Physical impairment by the Short Physical Performance Battery (SPPB) and cognitive dysfunction by the Mini-Mental State Examination in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC) were significantly associated with nonfatal toxicities, including grade 3 to 4 infections (SPPB, P = .024; MMSE-KC, P = .044), acute renal failure (SPPB, P = .013), and/or prolonged hospitalization (≥40 days) during induction chemotherapy (MMSE-KC, P = .005). Reduced physical function by SPPB and depressive symptoms by the Korean version of the short form of geriatric depression scales (SGDS-K) were significantly associated with inferior survival (SPPB, P = .027; SGDS-K, P = .048). Gait speed and sit-and-stand speed were the most powerful measurements for predicting survival outcomes. Notably, the addition of SPPB and SGDS-K, gait speed and SGDS-K, or sit-and-stand speed and SGDS-K significantly improved the power of existing survival prediction models. In conclusion, GA improved risk stratification for treatment decisions and may inform interventions to improve outcomes for older adults with AML. This study was registered at the Clinical Research Information Service as #KCT0002172.

Comparison of EUS-guided ablation and surgical resection for nonfunctioning small pancreatic neuroendocrine tumors: a propensity score-matching study.

BACKGROUND AND AIMS: Treatment strategies for small pancreatic neuroendocrine tumors (PNETs) <2 cm in size are still under debate. The feasibility and safety of EUS-guided ethanol ablation (EUS-EA) have been demonstrated. However, sample sizes in previous studies were small with no comparative studies on surgery. Therefore, we aimed to compare the safety and long-term outcomes of EUS-EA with those of surgery for the management of nonfunctioning small PNETs. METHODS: We retrospectively reviewed patients with PNETs who were managed by EUS-EA (from 2011 to 2018) and surgery (from 2000 to 2018) at Asan Medical Center. Propensity score matching (PSM) was performed to increase comparability. The primary outcome was early and late major adverse events (Clavien-Dindo grade ≥III) after treatment. Secondary outcomes were 10-year overall (OS) and disease-specific survival (DSS) rates, length of hospital stay, and development of endocrine pancreatic insufficiency. RESULTS: Of all patients, 97 and 188 patients were included in the EUS-EA and surgery groups, respectively. PSM created 89 matched pairs. EUS-EA was associated with a significantly lower rate of early major adverse events (0% vs 11.2%, P = .003). Late major adverse events occurred more frequently after surgery, with no significant difference between groups (3.4% vs 10.1%, P = .07). Both treatment modalities showed comparable 10-year OS and DSS rates. The length of hospital stay was significantly shorter in the EUS-EA group (4 days vs 14.1 days, P < .001), and endocrine pancreatic insufficiency was less common after EUS-EA than after surgery (33.3% vs 48.6%, P = .121). CONCLUSIONS: EUS-EA had fewer adverse events and a shorter hospital stay with similar OS and DSS rates compared with surgery, suggesting that EUS-EA may be a preferred alternative to surgical resection in selected patients with nonfunctioning small PNETs.

High failure rate after conservative treatment for recurrent shoulder dislocation without subjective apprehension on physical examination.

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.

Marrow stimulation procedures for high-grade cartilage lesions during surgical repair of medial meniscus root tear yielded suboptimal outcomes, whilst small lesions showed surgical eligibility.

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.

Haploidentical vs matched unrelated donor transplantation for acute myeloid leukemia in remission: A prospective comparative study.

Despite comparable outcomes of haploidentical transplants (Haplo-HSCT) with HLA-matched unrelated transplants (MUD-HSCT) in retrospective comparisons, few studies have prospectively compared Haplo-HSCT with MUD-HSCT in AML. Here, we prospectively compared the outcomes of Haplo-HSCT with MUD-HSCT for AML in remission (n = 110) to prove non-inferiority of overall survival in Haplo-HSCT. Both groups were well balanced in factors related to biological features of AML and measurable residual disease (MRD) status by Wilms' tumor gene 1 (WT1) assay. A unique, reduced-toxicity preparative regimen was used for Haplo-HSCT, whereas mostly-myeloablative regimen was for MUD-HSCT. Both groups showed similar patterns of neutrophil and platelet recovery, whereas delayed T-cell reconstitution in Haplo-HSCT was found compared with MUD-HSCT. No significant differences were found in acute or chronic graft-vs-host-disease (GVHD) and post-transplant infectious events with an exception of EBV or CMV infection, which occurred more frequently in Haplo-HSCT. After a median follow-up of 47 months, no significant differences in overall survival (65% vs 54%, P = .146), disease-free survival (67% vs 53%, P = .142), relapse (20% vs 21%, P = .858), non-relapse mortality (14% vs 26%, P = .103), or GVHD-free/relapse-free survival (54% vs 41%, P = .138) were observed for Haplo-HSCT vs MUD-HSCT. In multivariate analysis, WT1 expression before transplantation independently predicted relapse, resulting in inferior survival. Separate analysis of unenrolled patients (n = 110) who were excluded or refused to participate in this study showed consistent results with enrolled patients. This prospective study demonstrated the non-inferiority of Haplo-HSCT to MUD-HSCT for AML in remission, and validated the role of WT1 quantification as an MRD marker (ClinicalTrial.gov identifier: NCT01751997).

Low-dose thymoglobulin for prevention of chronic graft-versus-host disease in transplantation from an HLA-matched sibling donor.

Despite the proven efficacy of anti-T-cell or antithymocyte globulin (ATG) for chronic graft-versus-host disease (GVHD) prevention in transplantation from an unrelated donor, dosing protocols and the effects of ATG on relapse and infection remain controversial. In the setting of transplantation from an HLA-matched sibling (MSD-T), few randomized studies have been conducted. We conducted a prospective, single-center, open-label, randomized study of low-dose thymoglobulin (2.5 mg/kg) for chronic GVHD prevention. A total of 120 patients with acute leukemia were randomly assigned in a 1:1 ratio. After a median follow-up of 27 months, the cumulative incidence of chronic GVHD in the ATG and non-ATG groups was 25.0% and 65.4% (p < 0.001), respectively. The ATG group had an increased relapse rate compared with the non-ATG-group (20.0% vs. 9.3%; p = 0.055), with risks that differed according to cytogenetic subgroup (high-risk, 29.6% vs. 9.3%, p = 0.042; non-high-risk, 12.2% vs. 9.2%, p = 0.596). Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group (46.7% vs. 19.4%; p = 0.070), and the difference was significant in a cytogenetic non-high-risk subgroup (45.5% vs. 0%; p = 0.038). No differences were observed in other survival outcomes. Improved physical components in quality-of-life scores were observed in the ATG group at 12 months after transplantation. A higher rate of Epstein-Barr virus reactivation was observed in the ATG group (21.8% vs. 5.1%; p = 0.013), whereas no between-group differences for other complications. In conclusion, the low-dose thymoglobulin effectively prevented chronic GVHD in MSD-T, resulting in improvement in quality-of-life and cGRFS, whereas the necessity of caution for high-risk acute leukemia.

Contact Tracing during Coronavirus Disease Outbreak, South Korea, 2020.

We analyzed reports for 59,073 contacts of 5,706 coronavirus disease (COVID-19) index patients reported in South Korea during January 20-March 27, 2020. Of 10,592 household contacts, 11.8% had COVID-19. Of 48,481 nonhousehold contacts, 1.9% had COVID-19. Use of personal protective measures and social distancing reduces the likelihood of transmission.

Comparison of Myeloablative (CyTBI, BuCy) versus Reduced-Intensity (FluBu2TBI400) Peripheral Blood Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Pretransplant Low WT1 Expression.

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/104ABL 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 104ABL at transplantation.

Outcomes of Haploidentical Stem Cell Transplantation using Total Body Irradiation (600 cGy) and Fludarabine with Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia: A Prospective Phase II Study.

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.

Non-myeloablative matched sibling stem cell transplantation with the optional reinforced stem cell infusion for patients with hemoglobinopathies.

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 ß-thalassemia major (ß-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, ß-TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four ß-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 ß-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 ß-TM patients.

Role of pretransplant anti-thymocyte globulin in matched sibling donor stem cell transplantation after reduced intensity conditioning for myelodysplastic syndrome.

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.

The number of wire placement in the pancreatic duct and metal biliary stent as risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis.

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.

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea.

BACKGROUND: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. METHODS: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. RESULTS: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. CONCLUSION: The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome.

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.

WT1 Measurable Residual Disease Assay in Patients With Acute Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation: Optimal Time Points, Thresholds, and Candidates.

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.

Comparison of transplant-specific prognostic scoring systems in haploidentical transplantation for myelodysplastic syndrome.

OBJECTIVES: We intended to identify the predictive abilities of recently published transplant-specific prognostic scoring systems in patients with myelodysplastic syndrome (MDS) receiving haploidentical transplantation. METHODS: The outcomes of 73 patients with MDS receiving haploidentical transplantation were analyzed, according to the MTPSS, the TRI, and the CIBMTR scoring systems. RESULTS: The median age of patients at transplantation was 50 (range, 19-69) years. The IPSS-R cytogenetic risks of very good/good, intermediate, and poor/very poor were, respectively, observed in 35 (48.0%), 25 (34.2%), and 13 (17.8%) patients, including 4 (5.5%) with a monosomal karyotype. Pretransplant treatment failure and high (≥3) HCT-CI were observed in 30 (41.1%) and 35 (48.0%) patients, respectively. With survivor's median follow-up of 42.3 months, the overall survival rate at 4 years of all patients was 65.5% (95% CI, 52.4-75.9). The MTPSS (100%, 77.3%, 62.5%, and 42.0% at 4 years; P = .02) and the TRI (100%, 79.9%, 76.0%, and 17.1% at 4 years; P < .01) differentiate proportionally overall survival rates according to their 4 risk groups, whereas the CIBMTR scoring system did not (P = .17). CONCLUSIONS: Our results suggest the potential ability of the MPTSS and the TRI as prognostic tools for patients with MDS receiving haploidentical transplantation.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016.

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19-64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

Negative Impact of Unidirectional Host-versus-Graft Killer Cell Immunoglobulin-like Receptor Ligand Mismatch on Transplantation Outcomes after Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia.

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.

Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients.

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), and Lens culinaris agglutinin-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.

CD161(+) T cells as predictive markers for acute graft-versus-host disease.

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.