Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea.

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 next-generation sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly next-generation 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.

Molecular genetic testing enabled the diagnosis of otherwise undiagnosable cases of pyruvate kinase deficiency.

The gold standard for the diagnosis of pyruvate kinase (PK) deficiency, the most frequent red blood cell enzymopathy, is an enzymatic activity assay. However, this assay is rather unreliable in a clinical setting, often leading to misdiagnosis or missed diagnosis. This report presented the cases of two patients diagnosed with PK deficiency using molecular genetic testing, even though conventional laboratory tests, including the PK activity assay, failed to detect any abnormalities. Genetic analysis of the patients and their asymptomatic parents revealed the presence of variants in both alleles of the PKLR gene that were assessed as "likely pathogenic" or "pathogenic" in the form of compound heterozygotes. One of the mutations detected was common in both patients. Our results suggested that genetic testing might be required for the reliable diagnosis of suspected congenital hemolytic anemia cases displaying atypical presentation.

Erratum: Correction of Affiliations in the Article "Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study".

This corrects the article on p. e393 in vol. 35, PMID: 33258329.

High anemia prevalence in Korean older adults, an advent healthcare problem: 2007-2016 KNHANES.

BACKGROUND: Anemia is associated with high morbidity and mortality in older people. However, the prevalence and characteristics of anemia in older individuals are not fully understood, and national data on these aspects in older Korean adults are lacking. This study aimed to evaluate the prevalence and characteristics of anemia in older adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a nationwide cross-sectional epidemiological study conducted by the Korean Ministry of Health and Welfare. METHODS: Data from a total of 62,825 participants of the 2007-2016 KNHANES were compiled and analyzed to investigate differences in participant characteristics and potential risk factors for anemia. Differences in clinical characteristics of participants were compared across subgroups using the chi-square test for categorical variables and independent t-test for continuous variables. Univariate and multivariate analyses using logistic regression were performed to identify related clinical factors. RESULTS: The prevalence of anemia was higher in the population aged ≥65 years than in the younger population. Anemia was also more prevalent among females than among males, but this difference was not significant in people aged > 85 years. Being underweight, receiving a social allowance, living alone, and having comorbidities such as hypertension, rheumatoid arthritis, diabetes mellitus (DM), cancer, and chronic renal failure (CRF) were more common among older adults with anemia than among the population without anemia. In univariate and multivariate analyses, older age, female sex, underweight, and presence of comorbidities including rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia. CONCLUSIONS: This study revealed that age, female sex, underweight, and the presence of comorbidities such as rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia in older Korean adults. Further study on causal relationships between anemia and other variables in the older population is necessary.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

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.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study.

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, high-risk, 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.

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470).

Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: a hospital-based case control study.

BACKGROUND: Because the developing brain of a child is vulnerable to environmental toxins, even very low concentration of neurotoxin can affect children's neurodevelopment. Lead is a neurotoxic heavy metal which has the harmful effect on the striatal-frontal circuit of brain. This area of the brain is known to be closely related to attention deficit hyperactivity disorder (ADHD) pathophysiology. The primary objective of the present study was to investigate whether elevated blood lead concentration is a risk factor for ADHD. The secondary objective was to examine the association between blood lead concentration and symptom severity. METHODS: We conducted a frequency-matched, hospital-based case-control study with 114 medically diagnosed ADHD cases and 114 controls. The participants were matched for age and sex. The diagnoses of ADHD were assessed with semi-structured diagnostic interviews. The participants completed the continuous performance test (CPT), and their parents completed the ADHD-rating scale (ADHD-RS). Blood lead concentrations were measured by using graphite furnace atomic absorption spectrometry featuring Zeeman background correction. RESULTS: Children with ADHD exhibited blood lead concentrations that were significantly higher than those of the controls ( 1.90 ± 086 µg/dℓ vs. 1.59 ± 0.68 µg/dℓ, p = 0.003). The log transformed total blood lead concentration was associated with a higher risk of ADHD (OR: 1.60, 95 % CI: 1.04-2.45, p < 0.05). The analysis also revealed that the children with blood lead concentrations above 2.30 µg/dℓ were at a 2.5-fold (95 % CI: 1.09-5.87, p < 0.05) greater risk of having ADHD. After adjusting for covariates, our multivariate regression models indicated that blood lead concentrations were not significantly associated with ADHD-RS or CPT profiles among the ADHD cases. CONCLUSION: Even low blood lead concentrations are a risk factor for ADHD in children. This study warrants primary prevention policies to reduce the environmental lead burden. Future studies may be required to ascertain the effects of lead on symptom severity in ADHD.

Optimal time to start peripheral blood stem cell collection in children with high-risk solid tumors.

In order to clarify the optimal timing for peripheral blood stem cell (PBSC) collection, PBSC collection records of 323 children who were scheduled to undergo autologous stem cell transplantation from two study periods differing in the timing of PBSC collection were analyzed. In the early study period (March 1998 to August 2007, n=198), PBSC collection was initiated when the peripheral WBC count exceeded 1,000/µL during recovery from chemotherapy. Findings in this study period indicated that initiation of PBSC collection at a higher WBC count might result in a greater CD34(+) cell yield. Therefore, during the late study period (September 2007 to December 2012, n=125), PBSC collection was initiated when the WBC count exceeded 4,000/µL. Results in the late study period validated our conclusion from the early study period. Collection of a higher number of CD34(+) cells was associated with a faster hematologic recovery after transplant in the late study period. Initiation of PBSC collection at WBC count > 4,000/µL was an independent factor for a greater CD34(+) cell yield. In conclusion, PBSC collection at a higher WBC count is associated with a greater CD34(+) cell yield, and consequently a faster hematologic recovery after transplant.

A strategy for enhancing the engraftment of human hematopoietic stem cells in NOD/SCID mice.

To overcome the limitations of allogeneic hematopoietic stem cell transplantation (HSCT), we conducted a study to identify a strategy for enhancing hematopoietic stem cell (HSC) engraftment during HSCT. Co-transplantation experiments with mesenchymal stem cells (MSCs) derived from adult human tissues including bone marrow (BM), adipose tissue (AT), and umbilical cord blood (CB) were conducted. We showed that AT-MSCs and CB-MSCs enhanced the engraftment of HSCs as effectively as BM-MSCs in NOD/SCID mice, suggesting that AT-MSCs and CB-MSCs can be used as alternative stem cell sources for enhancing the engraftment and homing of HSCs. CB-MSCs derived from different donors showed different degrees of efficacy in enhancing the engraftment of HSCs. The most effective CB-MSCs showed higher proliferation rates and secreted more MCP-1, RANTES, EGF, and VEGF. Our results suggest that AT-MSCs and CB-MSCs could be alternative stem cell sources for co-transplantation in HSCT. Furthermore, in terms of MSCs' heterogeneity, characteristics of each population of MSCs are considerable factors for selecting MSCs suitable for co-transplantation with HSC.

Second allogeneic stem cell transplantation in hematologic malignancies: a single-center experience.

Patients with hematologic malignancies who relapse after their first hematopoietic stem cell transplantation tend to have poor prognoses. One option for these patients is a second allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there are few reports of second allo-HSCT therapy in children with relapsed hematologic malignancies. Patient outcomes in 27 individuals with acute leukemia who received at least 2 allo-HSCTs at the Samsung Medical Center between May 1997 and September 2010 were analyzed retrospectively. After a median follow-up of 33 months, 11 of 27 patients (40.7%) were alive and in stable remission. The 5-year overall survival rate for all 27 patients was 32.6%. There was no statistically significant difference in the survival rates of patients differing in their sex, the stem cell source, the donor type, or the presence of acute or chronic graft-versus-host disease. Remission before the second allo-HSCT was the only prognostic factor that influenced the survival rates (44.1% vs. 11.1%, P=0.009). Of 16 cases of mortality, 9 mortality cases (56.3%) were associated with relapse and 7 cases (43.7%) were associated with treatment-related mortality. Therefore, a second allo-HSCT offers the chance of stable remission for some patients with acute hematologic malignancies who relapse after their first allo-HSCT.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

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.

Iron chelation treatment with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors.

BACKGROUND: We evaluated whether iron chelation treatment during induction chemotherapy could safely reduce serum iron levels and thereby reduce the frequency of hepatic veno-occlusive disease (VOD) during high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in children with high-risk solid tumors. PROCEDURE: Children diagnosed with high-risk solid tumors between August 2008 and July 2009 were enrolled. Deferasirox treatment (25 mg/kg/day) was initiated when serum ferritin levels increased to more than 1,000 ng/ml during induction chemotherapy. Patients who were diagnosed with the same disease between April 2005 and June 2007 and treated in the same way without any iron chelation treatment formed the control group. Efficacy and toxicity of deferasirox treatment were compared between the two groups. RESULTS: Eighteen of 20 patients enrolled received deferasirox treatment. Deferasirox treatment was completed as scheduled in 11 (61.1%) of them without dose reduction or discontinuation. The serum ferritin levels prior to HDCT/autoSCT were lower in the deferasirox group than in the control group (median 1,268 ng/ml vs. 1,828 ng/ml, P < 0.001), although there was no difference in the RBC transfusion amount between the two groups. While 7 (17.9%) VODs developed during 39 HDCT/autoSCTs in the control group, there was no VOD during 40 HDCT/autoSCTs in the deferasirox group (P = 0.005). However, renal dysfunction (38.9%) including Fanconi syndrome (16.7%) was a frequently observed adverse effect of deferasirox treatment. CONCLUSIONS: Deferasirox treatment during induction chemotherapy reduces the frequency of VOD during HDCT/autoSCT. The development of renal dysfunction should be closely monitored during deferasirox treatment.

Iron overload during follow-up after tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma.

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34(+) cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34(+) cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34(+) cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

Korean clinical practice guidelines for the diagnosis of hereditary hemolytic anemia.

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.

Low-dose mitotane-induced neurological and endocrinological complication in a 5-year-old girl with adrenocortical carcinoma.

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.

Reduced-intensity allogeneic stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation.

BACKGROUND: To date, no effective curative option is available for children with neuroblastoma (NB) who failed tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). The present study evaluated the feasibility and efficacy of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) in six children with NB who failed tandem HDCT/autoSCT. PROCEDURE: A cyclophosphamide/fludarabine regimen was used as a conditioning for HLA-matched SCT, and ATG was added for haploidentical SCT. Peripheral blood stem cells from four HLA-matched donors and two haploidentical donors were transplanted. Immune suppression was rapidly tapered if graft-versus-host disease (GVHD) was absent. RESULTS: Regimen-related short-term toxicity was manageable, and complete donor chimerism was achieved in the early period after transplant. Grade I/II acute GVHD developed or was induced in all patients. Tumor response, attributed to a graft-versus-tumor (GVT) effect, was observed in two of six patients after induction of acute GVHD. The other four patients with significant tumor burden prior to transplant had tumor progression despite presence of GVHD. However, it was difficult to effectively reduce the tumor burden prior to transplant through the use of conventional treatment modalities. CONCLUSION: Although regimen-related short-term toxicity was manageable in intensively pretreated patients with NB, GVT effect was not sufficiently strong to control tumor progression in patients who had a significant tumor burden at transplant. Therefore, new treatment modalities to effectively reduce tumor burden prior to transplant in concert with post-transplant adjuvant treatment to enhance the GVT effect are needed to improve the outcome after RI alloSCT.

Correlation between chemokines released from umbilical cord blood-derived mesenchymal stem cells and engraftment of hematopoietic stem cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) enhance the engraftment of human hematopoietic stem cells (HSCs) when they are cotransplanted in animal and human studies. However, the type of MSCs that preferentially facilitate the engraftment and homing of HSCs is largely unknown. The authors categorized UCB-MSCs as the least-effective MSCs (A) or most-effective MSCs (B) at enhancing the engraftment of HSCs, and compared the gene expression profiles of various cytokines and growth factors in the UCB-MSC populations. The most-effective UCB-MSCs (B) secreted higher levels of several factors, including chemokine (C-X-C motif) ligand 12 (CXCL12), regulated upon activation, normal T cells expressed and secreted (RANTES), epithelial growth factor (EGF), and stem cell factor (SCF), which are required for the engraftment and homing of HSCs. By contrast, levels of growth-related oncogene (GRO), insulin-like growth factor-binding protein 1 (IGFBP1), and interleukin-8 (IL-8), which are associated with immune inflammation, were secreted at higher levels in UCB-MSCs (A). In addition, there were no differences between the transcripts of the 2 UCB-MSC populations after interferon-gamma (IFN-γ) stimulation, except for cyclooxygenase (COX)-1. Based on these findings, the authors propose that these chemokines may be useful for modulating these cells in a clinical setting and potentially for enhancing the effectiveness of the engraftment and homing of HSCs.

Korean parents' perceptions of the challenges and needs on school re-entry during or after childhood and adolescent cancer: a multi-institutional survey by Korean Society of Pediatric Hematology and Oncology.

BACKGROUND: For children and adolescents with cancer, going back to school is a key milestone in returning to "normal life." PURPOSE: To identify the support vital for a successful transition, we evaluated the parents' needs and the challenges they face when their children return to school. METHODS: This multi-institutional study was conducted by the Korean Society of Pediatric Hematology and Oncology. The written survey comprised 24 questions and was completed by 210 parents without an interviewer. RESULTS: Most parents (165 of 206) reported that their children experienced difficulties with physical status (n=60), peer relationships (n=30), academic performance (n=27), emotional/behavioral issues (n=11), and relationships with teachers (n=4) on reentering school. Parents wanted to be kept informed about and remain involved in their children's school lives and reported good parent-teacher communication (88 of 209, 42.1%). Parents reported that 83.1% and 44.9% of teachers and peers, respectively, displayed an adequate understanding of their children's condition. Most parents (197 of 208) answered that a special program is necessary to facilitate return to school after cancer therapy that offers emotional support (n=85), facilitates social adaptation (n=61), and provides tutoring to accelerate catch up (n=56), and continued health care by hospital outreach and school personnel (n=50). CONCLUSION: In addition to scholastic aptitude-oriented programs, emotional and psychosocial support is necessary for a successful return to school. Pediatric oncologists should actively improve oncology practices to better integrate individualized school plans and educate peers and teachers to improve health literacy to aid them in understanding the needs of children with cancer.

Iodine status and characteristics of Korean adolescents and their parents based on urinary iodine concentration: a nationwide cross-sectional study.

PURPOSE: Iodine is a major component of thyroid hormones. Both deficiency and excess of iodine are major risk factors for thyroid disease, making it important to accurately assess iodine level in the human body. Urinary iodine concentration (UIC) is a commonly used measure of iodine status. However, there is little research on iodine status and related characteristics in Korean adolescents. METHODS: Using data from the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI) for the years 2013-2015, we analyzed UIC and thyroid function test results in adolescents aged 10-18 years and their parents. We also investigated the influence of socioeconomic factors and family history of thyroid disease on iodine status. RESULTS: Mean UIC in Korean adolescents was 963.5±55.7 µg/L. Among evaluated subjects, 6.6%±1.0%, 29.8%±1.7%, and 63.9%±1.9% had low (UIC<100 µg/L), adequate (UIC: 100-299.9 µg/L), and excess (UIC≥300 µg/L) iodine concentrations, respectively. Based on regional trends, the incidence of iodine deficiency exceeded 10% in several regions, even though there was a dominance of regions with excess iodine. Parental UIC, female sex, average monthly income, and expenditure were all found to affect the iodine status of Korean adolescents. CONCLUSION: Although regional differences exist, the iodine status in Korean adolescents is mainly affected by the eating habits of their families and socioeconomic factors. Therefore, monitoring of iodine status is necessary in this population.