Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data.

PURPOSE: We aimed to determine the current application and survival trends of hematopoietic stem cell transplantation (HSCT) among Korean children and adolescents with cancer. MATERIALS AND METHODS: Data of patients aged < 20 years with KCD-10 (Korean Classifications of Diseases, 10th revision) C codes and specific designation codes were collected from the National Health Insurance Service database. Thirty claim codes for HSCT were included, and data from 2009 to 2019 were analyzed. RESULTS: The operational definition of pediatric cancer yielded an annual average of 2,000, with annual cases decreasing. In 2019, 221 HSCTs were performed, a decrease from the ten-year average of 276. Allografts outnumbered autografts with a ratio of 1.5:1. The source of allograft was bone marrow in 15% of patients in 2009; however, it substantially decreased to 3.3% in 2019. Furthermore, 70.5% of allogeneic HSCT used peripheral blood stem cell (PBSC) grafts, which increased to 89.3% by 2015. Cord blood utilization markedly decreased to 2.7% in 2018. The 5-year overall survival (OS) rate of all patients was 85.1%. Overall mortality decreased among patients who underwent recent HSCT, and they exhibited a higher 5-year OS rate. CONCLUSION: In Korea, the number of pediatric patients with cancer is declining; however, the ratio of transplants to all patients remains constant. Patients who recently underwent transplantation showed better survival rates, possibly due to HSCT optimization. Korea showed a substantially greater PBSC utilization in pediatric HSCT. An in-depth examination encompassing donor relations and cause of death with a prospective registry is required in future studies.

Clinical characteristics and treatment outcomes of children and adolescents with aggressive mature B-cell lymphoma: a single-center analysis.

Background: Aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common non-Hodgkin lymphoma in children. The outcome of chemotherapy for B-NHL has improved over decades. Methods: We reviewed 82 children and adolescents with B-NHL diagnosed at Asan Medical Center between 1993 and 2020. The D-COMP/COMP (daunomycin-cyclophosphamide, doxorubicin, vincristine, and prednisolone), Pediatric Oncology Group (POG)-9219/9315/9317, R-CHOP/CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone), and Lymphomes Malins B 89 (LMB89)/LMB96 regimens were administered. In 2018, rituximab was added to the LMB protocol (R-LMB) for advanced-staged Burkitt lymphoma (BL). The patients' clinical features and treatment outcomes were retrospectively analyzed. Results: The most common subtype was BL (61%), followed by diffuse large B-cell lymphoma (DLBCL) (35%). The median age was 7.8 (range, 1.3‒16.4) years, and the most frequently used regimen was French‒American‒British (FAB)/LMB96 (58 patients, 70.7%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 92.5% and 85.7%, respectively. The EFS rates of patients with BL and DLBCL were 90.0% and 79.3%, respectively. Among the FAB/LMB risk groups, group C (85.7%) had a significantly lower 5-year OS (P =0.037). Eleven events occurred (6 relapses, 3 deaths, and 2 secondary malignancies) during the median follow-up of 7.1 (range, 3.7‒118.5) months. Two patients treated with R-LMB had good outcomes without complications. Conclusion: Various treatment regimens have favorable outcomes in pediatric patients with B-NHL. However, further studies are needed to improve survival in high-risk patients. In addition, careful monitoring for acute toxicity or secondary malignancy due to intensive multidrug chemotherapy is required.

Case Report: Mevalonic Aciduria Complicated by Acute Myeloid Leukemia After Hematopoietic Stem Cell Transplantation.

Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Here, we report a case of an infant who showed severe recurrent systemic inflammation and was diagnosed with MA. Although she responded to steroids, her symptoms relapsed after the dose was tapered, and organ deterioration occurred. Therefore, at the age of 11 months, HCT from a matched, unrelated donor was performed for curative treatment. However, at 50 days after transplantation, acute myeloid leukemia was diagnosed, which was chemo-refractory. A second HCT from her haploidentical father was performed to treat the acute myeloid leukemia, but the patient died of sepsis on day 4 after transplantation. This is the first report of malignancy following HCT for MA. Our findings suggest that normalizing the mevalonate pathway after HCT in patients with MKD impacts patients differently depending on the clinical spectrum and severity of disease.

Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder caused by the clonal expansion of myeloid precursors that differentiate into CD1a+/CD207+ cells in the lesion. Advances in genomic sequencing techniques have improved our understanding of the pathophysiology of LCH. Activation of the mitogen-activated protein kinase (MAPK) pathway is a key molecular mechanism involved in the development of LCH. Recurrent BRAF mutations and MAP2K1 mutations are the major molecular alterations involved in the activation of the MAPK pathway. Recent studies have supported the "misguided myeloid differentiation model" of LCH, where the extent of disease is defined by the differentiation stage of the cell in which the activating somatic MAPK mutation occurs, suggesting LCH. Several studies have advocated the efficacy of targeted therapy using BRAF inhibitors with a high response rate, especially in patients with high-risk or refractory LCH. However, the optimal treatment scheme for children remains unclear. This review outlines recent advances in LCH, focusing on understanding the molecular pathophysiology, emerging targeted therapy options, and their clinical implications.

Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis.

BACKGROUND: Lymphoblastic lymphoma (LBL) is the second most common subtype of pediatric non-Hodgkin lymphoma. Modified treatments derived from the LSA2-L2 regimen resulted in encouraging survival, but toxicities and long-term sequelae have been problematic. At present, the acute lymphoblastic leukemia (ALL)-type protocol has demonstrated efficacy in LBL. We analyzed the outcomes of children and adolescents with LBL treated with various regimens. METHODS: From 1991‒2018, this study enrolled 63 patients diagnosed with LBL at Asan Medical Center. Medical records were retrospectively analyzed. RESULTS: Among 63 patients, most patients (38.1%) presented with stage IV at diagnosis, and two had central nervous system (CNS) involvement. At a median follow-up of 160 months, the 5-year event free survival (EFS), overall survival (OS), and relapse free survival (RFS) were 68.8%, 79.3%, and 71.3%, respectively. Among 61 patients who received chemotherapy, 27 patients (44.3%) received the NY protocol, and 14 (23.0%) received the ALL-type protocol. There was no significant difference in 5-yr OS (85.2%/78.6%), EFS (73.5%/78.6%), and RFS (73.5%/78.6%) between the NY and ALL protocol groups, regardless of immunophenotype. Thirteen patients (21.3%) received prophylactic cranial radiotherapy with no difference in the incidence of CNS relapse based on irradiation. CONCLUSION: This study showed no difference in outcome between the NY and ALL-type protocols, regardless of stage or immunophenotype. In addition to improving the effectiveness of treatment, it is necessary to continuously appraise the appropriate chemotherapy regimen, considering toxicities and long-term prognosis, for pediatric LBL.

The association between Staphylococcus aureus nasal colonization and symptomatic infection in children in Korea where ST72 is the major genotype: A prospective observational study.

This study was performed to investigate the concordance in terms of molecular characteristics and antimicrobial susceptibility between colonizing and clinical Staphylococcus aureus isolates obtained from children in Korea, where ST72 is the major genotype.This was a prospective observational descriptive study of culture-confirmed S aureus infections obtained from children ≤18 years old admitted to Asan Medical Center Children's Hospital in Seoul, Korea, from March 2014 to April 2015. Molecular studies including multilocus sequence typing (MLST), SCCmec typing, polymerase chain reaction amplification of the Panton-Valentine leukocidin (PVL) genes, and antibiotic susceptibility tests were performed on S aureus isolates obtained from nares and clinical specimens.During the study period, 126 clinically significant S aureus infections were identified. Nasal swab cultures were made from 113 of the 126 children, and 46.0% (52/113) showed S aureus colonization. The overall concordance between colonizing and clinical isolates by methicillin susceptibility was 94.2% (49/52); all 3 discordant cases were HA-MSSA cases with nasal MRSA. Among the 37 pairs of colonizing and clinical S aureus isolates included in the genotyping analysis, ST72-SCCmec type IV was the most prevalent clone and the PVL genes were positive in 2 patients. Among the 31 pairs of healthcare-associated cases, concordance rates by methicillin susceptibility and sequence type (ST) were 90.3% (28/31) and 84% (26/31), respectively. For the 6 pairs of community-associated (CA) S aureus including 3 CA-MRSA cases, 100% concordance was observed by methicillin susceptibility and ST.The concordance between isolates obtained from children who required medical services was relatively high in Korean children where ST72-SCCmec type IV is the predominant clone as the colonizer and the pathogen. It is suggested that decolonization and continuous care to prevent transmission could be effective in managing and preventing both HA- and CA-SA infections in our setting.

Recent change in congenital syphilis in Korea: Retrospective 10 year study.

BACKGROUND: This study was conducted to evaluate recent clinical and anthropologic features of neonates with reactive serology for syphilis and their mothers from three institutions in Korea over an 11-year-period. METHOD: The medical records of 20 neonates with reactive serology for syphilis and their mothers at three centers (Kyung Hee University Hospital, Kyung Hee University Hospital at Gangdong, and Korea Electric Power Corporation Hospital) seen between January 2000 and December 2010 were reviewed retrospectively. RESULTS: Among 20 mothers, 16 (80%) were native Korean and four (20%) were foreign-born immigrants. Two mothers (10%) were unmarried. The annual distribution of cases was three (15%) in 2000, one each (5%) in 2005 and 2006, respectively, two each (10%) in 2007 and 2008, respectively, six (30%) in 2009, and five (25%) in 2010. Just over half (55%) occurred across 2009 and 2010. All neonates, by definition, were diagnosed with presumptive congenital syphilis (CS). Among the neonates, four had positive cerebrospinal fluid venereal disease research laboratory test, and three exhibited symptoms and signs. CONCLUSIONS: In three centers in Seoul, Korea, the observed number of CS cases was higher in 2009 and 2010 than in previous years. This finding is consistent with a trend toward increasing prevalence of international marriage and suggests that more meticulous screening of CS is needed.

Cognitive function in childhood epilepsy: importance of attention deficit hyperactivity disorder.

BACKGROUND AND PURPOSE: To determine how cognitive function is related to epilepsy classification and comorbid attention deficit hyperactivity disorder (ADHD) in children with newly diagnosed epilepsy of genetic or unknown etiology. METHODS: The medical records of children aged 6-16 years with newly diagnosed epilepsy of genetic or unknown etiology were reviewed retrospectively. The Korean Education Development Institute-Wechsler Intelligence Scale for Children and the Comprehensive Attention Test were used to evaluate intelligence and attention/executive function, respectively. RESULTS: The data of a total of 149 children, 103 with focal seizures and 46 with generalized seizures, were reviewed. The prevalence of ADHD was 49.2% (59 out of 120 examined patients), and ADHD patients exhibited significantly worse auditory selective attention, flanker test results, and spatial working memory. Patients with generalized seizures exhibited significantly worse auditory selective and sustained attention than patients with focal seizures. In patients with generalized seizures, sustained attention, flanker test findings, and spatial working memory were found to be affected by ADHD, and auditory selective and sustained attention were significantly worse in patients with benign childhood epilepsy with centrotemporal spikes and ADHD than in their counterparts without ADHD. CONCLUSIONS: Cognitive processes are affected by seizure type and comorbid ADHD. Proper characterization of these neuropsychiatric impairments may allow earlier intervention during the disease course.

Rapid fecal cytokeratin-19 test and fecal occult blood test in screening for gastrointestinal diseases.

To evaluate the screening power of the fecal cytokeratin-19 test (CK-19) and the fecal occult blood test (FOBT), we performed rapid fecal CK-19 and FOBT tests on 515 stool samples from patients with various GI diseases and 814 stool samples from control patients. The rapid fecal CK-19 test (developed by DiNonA Research Institute, Seoul, Korea) is based on gold immunochromatography and has a sensitivity of 1 ng/ml. The positive rate of the FOBT was 2.1% in controls, 14.0% in GI cancer patients, 3.5% in GI inflammation patients, 11.7% in bone marrow transplant (BMT) patients, and 6.0% in childhood diarrhea patients. Except for the GI inflammation patients, the patients' positive rates for FOBT were all higher than the controls (p <0.05). The positive rate of the fecal CK-19 test was 8.2% in controls, 42.1% in GI cancer patients, 66.0% in GI inflammation patients, 84.8% in BMT patients, and 19.9% in childhood diarrhea patients. In all of the patient groups, positive rates for the CK-19 test were higher than in the controls (p <0.05). The fecal CK-19 test was more frequently positive (42.1%) in GI cancer patients than the FOBT; if both tests were used, the sensitivity was 49.1%. The fecal CK-19 test (but not the FOBT) gave a higher positive rate in GI inflammation patients than the controls, suggesting that the CK-19 test could serve as a screening test for GI inflammation. The highest positive rate of the fecal CK-19 test was found in the BMT group, indicating that significant GI epithelial desquamation had occurred. Although the positive rate of the fecal CK-19 test in childhood diarrhea patients was higher than in the controls, it was much lower than in adults with GI inflammatory disease. Evidently, children with GI inflammation do not desquamate as much intestinal epithelium as adult patients with GI inflammation. This study shows that the rapid fecal GK-19 test, used in conjunction with the FOBT, may be a valuable screening technique for GI diseases and can assist physicians in the differential diagnosis of GI diseases.