PURPOSE: This prospective pilot study is a part of the Korean NIH's effort to characterize con- genital anomalies and genetic disorders in Korea and to establish a National Genetic Database. METHODS: This population-based study was conducted at all hospitals that deliver in the province of Suwon; a total of 39 hospitals from May 1, 1997 to April 30, 1999 for a two-year period. All outcome of pregnancies, including liveborn, stillborn, and TOP over 20wks gestation were subjects of this study for the presence of major congenital anomalies. Delivery records of each hospital and pediatric records of one tertiary hospital were collected and analyzed. RESULTS: The total number of pregnancy was 30,319 yielding 30,653 deliveries, including 269 still-born and 27 TOPs. The overall incidence of congenital anomalies was 1.2Yo(366 cases among 30,653 deliveries) with 0.5Yo from primary hospital, 1.4Yo of general hospital deliveries and 4.5Yo of tertiary hospital deliveries. The incidences of selective major congenital anomalies per 1,000 deliveries were 0.82 for Down syndrome, 1.79 for cleft lip with or without cleft palate, and 0.39 for open neural tube defect. CONCLUSION: This pilot study represented the first community-based population data on congenital anomalies in Korea, differing from previous studies based on selective population of relative high-risk population from tertiary hospital delivery. Search for congenital anomalies among cohort by reviewing pediatric records yielded 38Yo of total anomalies, indicating the importance of combining both delivery and pediatrics records in generating accurate data for the incidence of congenital anomalies. (J Korean Pediatr Soc 2000;43:738-745)
Cleft Lip ; Cleft Palate ; Cohort Studies ; Congenital Abnormalities* ; Databases, Genetic ; Down Syndrome ; Epidemiologic Studies* ; Gyeonggi-do ; Hospitals, General ; Incidence ; Korea ; Neural Tube Defects ; Parturition* ; Pediatrics ; Pilot Projects* ; Pregnancy ; Prospective Studies* ; Tertiary Care Centers

BACKGROUND: A change in urine output has been recently recognized as a valuable biomarker of acute kidney injury that is associated with mortality in critically ill patients. We investigated the prognostic impact of oliguria for survival outcomes in multiple myeloma (MM) patients presenting with renal impairment (RI). METHODS: Retrospective data on 98 patients with MM and RI, who received initial treatment with novel therapies, were analyzed. Oliguria was defined as a urine output of <0.5 mL/kg/h. RESULTS: The baseline median eGFR was 39.7 mL/min (range, 5.1-59.8). Achievement of renal complete response (CR) was observed in 39.8% of patients. Nine patients (9.2%) presented with oliguria at initial diagnosis, and 4 initially required dialysis. Over a median follow-up period of 17.1 months (range, 1.7-100.0), the median overall survival (OS) was 38.7 months (95% CI 25.0-52.5). Multivariate analyses indicated that oliguria at diagnosis [hazard ratio (HR) 3.628, 95% CI 1.366-9.849, P=0.011], and thrombocytopenia <100x10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival. CONCLUSION: Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.
Acute Kidney Injury ; Critical Illness ; Diagnosis ; Dialysis ; Follow-Up Studies ; Humans ; Mortality* ; Multiple Myeloma* ; Multivariate Analysis ; Oliguria* ; Renal Insufficiency ; Retrospective Studies ; Thrombocytopenia

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Area Under Curve ; Child ; Dyspnea/etiology ; Female ; Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality ; Hemolysis ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases/complications/diagnosis ; L-Lactate Dehydrogenase/metabolism ; Male ; Middle Aged ; Odds Ratio ; ROC Curve ; Registries ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Thromboembolism/complications/diagnosis ; Young Adult

BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.
Cell Transplantation ; Comorbidity ; Consensus ; Cytogenetics ; Cytotoxins ; Hematology* ; Humans ; Korea ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Prognosis ; Protein-Tyrosine Kinases ; Risk Factors ; Transplants ; Treatment Outcome ; Dasatinib ; Imatinib Mesylate

BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.
Anemia, Aplastic* ; Cohort Studies* ; Flow Cytometry ; Follow-Up Studies ; Hemoglobinuria, Paroxysmal* ; Hemolysis ; Humans ; Prospective Studies*

BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. RESULTS: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.
Administration, Intravenous ; Adult ; Antiviral Agents/*administration & dosage/adverse effects ; BK Virus/*drug effects/immunology ; Cystitis/diagnosis/*drug therapy/immunology/virology ; Cytosine/administration & dosage/adverse effects/*analogs & derivatives ; Drug Administration Schedule ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Male ; Organophosphonates/*administration & dosage/adverse effects ; Polyomavirus Infections/diagnosis/*drug therapy/immunology/virology ; Retrospective Studies ; Time Factors ; Transplantation, Homologous ; Treatment Outcome ; Tumor Virus Infections/diagnosis/*drug therapy/immunology/virology ; Viral Load

BACKGROUND: The presence of FLT3 internal tandem dupulication (FLT3/ITD) in patients with acute myeloid leukemia (AML) with normal karyotype was investigated in order to evaluate its clinical and prognostic significance. METHODS: The FLT3/ITD was studied by PCR assay in bone marrow samples obtained from 123 patients at diagnosis. Ninety patients who received intensive induction chemotherapy were evaluated. RESULTS: Of total 123 patients, forty-seven (38.2%) demonstrated the aberrant FLT3/ITD. Patients with FLT3/ITD had significantly higher leukocyte counts at presentation than did patients without FLT3/ITD (P=0.04). By multivariate analysis, the FLT3/ITD was an independent prognostic factor of leukemic-free survival (LFS) (P=0.01) in AML patients with normal karyotype. CONCLUSION: This study demonstrated that the presence of the FLT3/ITD was a significant factor for poor prognosis in AML patients with normal karyotype.
Bone Marrow ; Diagnosis ; Humans ; Induction Chemotherapy ; Karyotype* ; Leukemia, Myeloid, Acute* ; Leukocyte Count ; Multivariate Analysis ; Polymerase Chain Reaction ; Prognosis

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.