Purpose: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. Results: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. Conclusion The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Background: Few studies have examined the incidence of chronic kidney disease (CKD) and metabolic syndrome (MS) and their combined prognostic effects in adult congenital heart disease (ACHD). Our aims were to identify the incidence and prognostic implications of CKD and MS in ACHD. Methods: This is retrospective cohort study. We included 2,462 ACHD ≥ 20 years of age who were treated at a tertiary hospital in Korea from 2006 to 2018. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m 2 . MS was diagnosed based on the presence of abnormal metabolic parameters: blood sugar level, obesity, dyslipidemia, and hypertension. The primary outcome was all-cause mortality from 2006 through 2019 using data from the Ministry of the Interior and Safety in Korea. Results: The incidence of CKD and MS in ACHD was 7.6% and 35.9%, respectively. The coexistence rate of CKD and MS was 4.6%. Although MS was not independently associated with mortality in the multiple analysis (adjusted hazard ratio [aHR], 1.07; 95% confidence interval [CI], 0.79–1.46), it was closely related to the presence of CKD (adjusted odds ratio, 2.62; 95% CI, 1.89–3.63). ACHD patients with CKD had a significantly increased risk of mortality compared with those without CKD (aHR, 2.84; 95% CI, 2.00–4.04). Conclusions In patients with ACHD, the distribution of MS is higher, and both MS and its components were associated with CKD. Given the CKD was independently associated with mortality, close monitoring and management of renal dysfunction and metabolic parameters in ACHD patients is needed.

Background: Few studies used nationwide data to assess the survival rates (SRs) and death risk for idiopathic pulmonary arterial hypertension (IPAH; ICD-10 I27.0) in Korea. Methods: IPAH data (N = 9,017; female:male = 6:4) were collected from the National Health Insurance Service in Korea, from 2006 through 2017. The data consisted of primary diagnoses related to IPAH. The Kaplan–Meier method and Cox proportional-hazards analyses were carried out. Results: The mean age was 62.3 (± 19.4) years, 64.2 (± 18.9) years in female and 59.4 (± 19.8) years in male (P < 0.001). The one-, three-, five- and 10-year SRs for IPAH were 89.0%, 79.8%, 72.3% and 57.0%, respectively. The adjusted hazard ratio (HR) of IPAH was 1.81 (95% confidence interval [CI], 1.26–2.59) in 60–69 age group, 3.42 (95% CI, 2.40–4.87) in 70–79, and 7.73 (95% CI, 5.43–11.0) in 80s. Other risk factors were male, low-income status, diabetes, myocardial infarction, atrial fibrillation, ischemic stroke, hemorrhagic stroke, and malignant neoplasm. Conclusion The 10-year SR of IPAH was 57% in Korea. The HR for IPAH was significantly high in patients with older age and other risk factors.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Objective: The clinical course of an individual patient with heart failure is unpredictable with left ventricle ejection fraction (LVEF) only. We aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived myocardial fibrosis extent and to determine the cutoff value for event-free survival in patients with non-ischemic cardiomyopathy (NICM) who had severely reduced LVEF. Materials and Methods: Our prospective cohort study included 78 NICM patients with significantly reduced LV systolic function (LVEF < 35%). CMR images were analyzed for the presence and extent of late gadolinium enhancement (LGE). The primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, heart transplantation, implantable cardioverter-defibrillator discharge for major arrhythmia, and hospitalization for congestive heart failure within 5 years after enrollment. Results: A total of 80.8% (n = 63) of enrolled patients had LGE, with the median LVEF of 25.4% (19.8–32.4%). The extent of myocardial scarring was significantly higher in patients who experienced MACE than in those without any cardiac events (22.0 [5.5–46.1] %LV vs. 6.7 [0–17.1] %LV, respectively, p = 0.008). During follow-up, 51.4% of patients with LGE ≥ 12.0 %LV experienced MACE, along with 20.9% of those with LGE ≤ 12.0 %LV (log-rank p = 0.001). According to multivariate analysis, LGE extent more than 12.0 %LV was independently associated with MACE (adjusted hazard ratio, 6.71; 95% confidence interval, 2.54–17.74; p < 0.001). Conclusion In NICM patients with significantly reduced LV systolic function, the extent of LGE is a strong predictor for longterm adverse cardiac outcomes. Event-free survival was well discriminated with an LGE cutoff value of 12.0 %LV in these patients.

Background: The number of adults with congenital heart disease (ACHD) with atrial fibrillation (AF) is expected to increase. We sought to assess the impact of AF on survival in Korean ACHD. Methods: Records of AF in ACHD were extracted from the records of the Korea National Health Insurance Service from 2006 through 2015. Multiple Cox proportional hazards analyses were carried out after adjustment for age, sex, income level, AF, and comorbidities.Survival rates (SRs) with and without AF were compared. The death records from 2006 through 2016 were included. Results: A total of 3,999 ACHD had AF (51.4% were male) and 62,691 ACHD did not have AF (43.5% were male); the proportion of ACHD who were 60 years and older was 53.0% and 27.0% in those with and without AF, respectively (P < 0.001). The age-standardized incidence rate for AF was 1,842.0 persons per 100,000 people in the Korean general population from 2006 through 2015. For AF in ACHD, it was 5,996.4 persons per 100,000 ACHD during the same period, which was higher than that in the general population (P< 0.001). Significantly higher proportion of death (20.9%) occurred in ACHD with AF than without AF (8.3%) (P< 0.001). The adjusted hazard ratio for AF of death in ACHD was 1.39 (95% confidence interval, 1.29– 1.50). The ten-year SR of ACHD with AF was 69.7% whereas it was 87.5% in non-AF (P < 0.001). Conclusion In ACHD, AF occurs more frequently and has a worse prognosis than seen in the non-valvular general population in Korea. AF is associated with increased death in ACHD, especially with aging.

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). Conclusion Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.