Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges.Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing nextgeneration sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly nextgeneration sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context.

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Mitotane is an adrenolytic drug that exhibits therapeutic effects within a narrow target range (14–20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair who was diagnosed with an adrenal mass that was subsequently excised. The pathological finding was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was recommended. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also administered. However, the patient exhibited elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty concentrating. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane level is elevated. Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by high mitotane level. The mitotane decreased to subtherapeutic level several months after its discontinuation, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient, indicating that the drug dose should be individualized with frequent monitoring of the therapeutic level.

Although the prevalence of hereditary hemolytic anemia (HHA) is relatively low in Korea, it has been gradually increasing in recent decades due to increment in the proportions of hemoglobinopathies from immigrants of South East Asia, raising awareness of the disease among clinicians, and advances in diagnostic technology. As such, the red blood cell (RBC) Disorder Working Party (WP), previously called HHA WP, of the Korean Society of Hematology (KSH) developed the Korean Standard Operating Procedures (SOPs) for the diagnosis of HHA in 2007. These SOPs have been continuously revised and updated following advances in diagnostic technology [e.g., flow cytometric osmotic fragility test (FOFT) and eosin-5-maleimide (EMA) binding test], current methods for membrane protein or enzyme analysis [e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC)], and molecular genetic tests using next-generation sequencing (NGS). However, the diagnosis and treatment of HHA remain challenging as they require considerable experience and understanding of the disease. Therefore, in this new Korean Clinical Practice Guidelines for the Diagnosis of HHA, on behalf of the RBC Disorder WP of KSH, updated guidelines to approach patients suspected of HHA are summarized. NGS is proposed to perform prior to membrane protein or enzyme analysis by LC-MS/MS, UPLC-MS/MS or HPLC techniques due to the availability of gene testing in more laboratories in Korea. We hope that this guideline will be helpful for clinicians in making diagnostic decisions for patients with HHA in Korea.

Purpose: To identify the differences in features between children with urinary tract infection (UTI) caused by extended-spectrum beta-lactamases (ESBL)-positive and -negative Escherichia coli, and analyze risk factors for the former infection. Methods: We reviewed medical records of children younger than 36 months with E. coli UTI who visited the emergency department from January 2012 through January 2019. Differences in variables regarding clinical, laboratory, and microbiologic (i.e., ESBL-positive E. coli on urine culture) features, and outcomes between the ESBL-positive and -negative groups were identified. Factors associated with ESBL-positive E. coli infection were analyzed by logistic regression. Results: The children were classified into the ESBL-positive (n = 151) and -negative (n = 40) groups. The former group showed higher frequency of prior UTI (P = 0.038) without other differences between the groups. The median counts of white blood cells, absolute neutrophils, and absolute lymphocytes were higher in the ESBL-positive group than in the other group (P = 0.009, 0.022, and 0.027, respectively). The former group showed longer median hospital length of stay (11.0 days [interquartile range, 8.9-12.0] vs. 6.0 [5.0-7.0]; P < 0.001), and more frequent recurrence per child (3.0 [2.5-3.0] vs. 1.0 [1.0-1.75]; P = 0.047) and presence of vesicoureteral reflux (27.5% vs. 13.2%; P = 0.001). Logistic regression showed leukocytosis (odds ratio, 12.85; 95% confidence interval, 1.04-157.69) and vesicoureteral reflux (4.00; 1.19-13.43) as the factors for ESBL-positive E. coli infection. Conclusion The ESBL-positive group showed significantly higher leukocyte count and rate of vesicoureteral reflux than the ESBL-negative group. For children with these features, empirical antibiotics should be chosen in consideration of the resistant bacteria.

Purpose: To identify the differences in features between children with urinary tract infection (UTI) caused by extended-spectrum beta-lactamases (ESBL)-positive and -negative Escherichia coli, and analyze risk factors for the former infection. Methods: We reviewed medical records of children younger than 36 months with E. coli UTI who visited the emergency department from January 2012 through January 2019. Differences in variables regarding clinical, laboratory, and microbiologic (i.e., ESBL-positive E. coli on urine culture) features, and outcomes between the ESBL-positive and -negative groups were identified. Factors associated with ESBL-positive E. coli infection were analyzed by logistic regression. Results: The children were classified into the ESBL-positive (n = 151) and -negative (n = 40) groups. The former group showed higher frequency of prior UTI (P = 0.038) without other differences between the groups. The median counts of white blood cells, absolute neutrophils, and absolute lymphocytes were higher in the ESBL-positive group than in the other group (P = 0.009, 0.022, and 0.027, respectively). The former group showed longer median hospital length of stay (11.0 days [interquartile range, 8.9-12.0] vs. 6.0 [5.0-7.0]; P < 0.001), and more frequent recurrence per child (3.0 [2.5-3.0] vs. 1.0 [1.0-1.75]; P = 0.047) and presence of vesicoureteral reflux (27.5% vs. 13.2%; P = 0.001). Logistic regression showed leukocytosis (odds ratio, 12.85; 95% confidence interval, 1.04-157.69) and vesicoureteral reflux (4.00; 1.19-13.43) as the factors for ESBL-positive E. coli infection. Conclusion The ESBL-positive group showed significantly higher leukocyte count and rate of vesicoureteral reflux than the ESBL-negative group. For children with these features, empirical antibiotics should be chosen in consideration of the resistant bacteria.

Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. Methods: We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. Results: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. Conclusion In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Background: Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

PURPOSE: Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients. MATERIALS AND METHODS: Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected. RESULTS: Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis. CONCLUSION: Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.
Anthracyclines ; Cardiotoxicity ; Dexrazoxane ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Korea ; Multivariate Analysis ; Neoplasms, Second Primary ; Risk Factors* ; Stem Cell Transplantation