Optimal Use and Need for Therapeutic Drug Monitoring of Teicoplanin in Children: A Systematic Review

Background@#Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant Staphylococcus aureus. Despite some comparable advantages, there is no guideline or clinical recommendation for teicoplanin in the pediatric population, unlike vancomycin where abundant studies and the recently revised guideline on therapeutic drug level monitoring (TDM) exist. @*Methods@#The systematic review was performed in accordance with the preferred reporting items for systematic reviews. Two authors (JSC and SHY) searched PubMed, Embase, and Cochrane Library databases using relevant terms independently. @*Results@#Fourteen studies were finally included with a total of 1,380 patients. TDM was available in 2,739 samples collected in the nine studies. Dosing regimens varied widely, and eight studies used recommended dosing regimens. Timing for measuring TDM was mostly 72–96 hours or longer after the initiation of the first dose, which was expected to be a steadystate. The majority of studies had target trough levels of 10 µg/mL or above. Three studies reported that the clinical efficacy and treatment success rate of teicoplanin was 71.4%, 87.5%, and 88%. Adverse events associated with teicoplanin use were described in six studies with a focus on renal and/or hepatic impairment. Except for one study, no significant relation was noted between the incidence of adverse events and trough concentration. @*Conclusion@#Current evidence on teicoplanin trough levels in pediatric populations is insufficient due to heterogeneity. However, target trough levels with favorable clinical efficacy are achievable by recommended dosing regimen in the majority of patients.

Chronic Recurrent Multifocal Osteomyelitis Associated With Inflammatory Bowel Disease Successfully Treated With Infliximab

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener’s disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn’s disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

The Changes in Epidemiology of Imipenem-Resistant Acinetobacter baumannii Bacteremia in a Pediatric Intensive Care Unit for 17 Years

Background@#Acinetobacter baumannii infections cause high morbidity and mortality in intensive care unit (ICU) patients. However, there are limited data on the changes of longterm epidemiology of imipenem resistance in A. baumannii bacteremia among pediatric ICU (PICU) patients. @*Methods@#A retrospective review was performed on patients with A. baumannii bacteremia in PICU of a tertiary teaching hospital from 2000 to 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST), and polymerase chain reaction for antimicrobial resistance genes were performed for available isolates. @*Results@#A. baumannii bacteremia occurred in 27 patients; imipenem-sensitive A. baumannii (ISAB, n = 10, 37%) and imipenem-resistant A. baumannii (IRAB, n = 17, 63%). There was a clear shift in the antibiogram of A. baumannii during the study period. From 2000 to 2003, all isolates were ISAB (n = 6). From 2005 to 2008, both IRAB (n = 5) and ISAB (n = 4) were isolated. However, from 2009, all isolates were IRAB (n = 12). Ten isolates were available for additional test and confirmed as IRAB. MLST analysis showed that among 10 isolates, sequence type 138 was predominant (n = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. Of 27 bacteremia patients, 11 were male (41%), the median age at bacteremia onset was 5.2 years (range, 0–18.6 years). In 33% (9/27) of patients, A. baumannii was isolated from tracheal aspirate prior to development of bacteremia (median, 8 days; range, 5–124 days). The overall case-fatality rate was 63% (17/27) within 28 days. There was no statistical difference in the case fatality rate between ISAB and IRAB groups (50% vs. 71%; P = 0.422). @*Conclusion@#IRAB bacteremia causes serious threat in patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial for managing IRAB infection in PICU.

A Case with Multiple Fungal Coinfections in a Patient who Presented with Pancoast Syndrome

Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.

Influenza Vaccine Effectiveness in Children at the Emergency Department during the 2018-2019 Season: the First Season School-aged Children Were Included in the Korean Influenza National Immunization Program

Background@#For the 2018–2019 season, the national influenza immunization program expanded to cover children aged from 6 months to 12 years in Korea. This study aimed to analyze vaccine effectiveness (VE) against influenza in children visiting the pediatric emergency room at a tertiary hospital during the 2018-2019 season. @*Methods@#Patients tested for influenza antigens from October 1st 2018 to May 31st 2019 at the pediatric emergency room of Samsung Medical Center were included. Patients' influenza antigen test results, influenza vaccination history, and underlying medical conditions were reviewed retrospectively. VE was estimated from the test-negative design study. @*Results@#Among the 2,901 visits with influenza test results 1,692 visits of 1,417 patients were included for analysis. Among these 1,417 patients, 285 (20.1%) were positive (influenza A, n = 211, 74.0%; influenza B, n = 74, 26.0%). The VE in all patients was 36.4% (95% confidence interval [CI], 13.9 to 53.1). The VE for influenza A was 37.6% (95% CI, 12.6 to 55.5) and VE for influenza B was 24.0% (−38.5 to 58.3). The VE in the age group 6 months to 12 years was significant with a value of 35.6% (95% CI, 10.5 to 53.7); it was not statistically significant in the age group 13 to 18 years. In a multivariate logistic regression model, patients who received an influenza vaccination were less likely to get influenza infection (OR, 0.6; 95% CI, 0.4 to 0.8; P = 0.001), with significant confounding factors such as age group 13 to 18 years (OR, 0.5; 95% CI, 0.3 to 0.8; P = 0.003) and underlying hematology-oncology disease (OR, 0.3;95% CI, 0.1 to 0.6; P = 0.002). @*Conclusion@#We report moderate effectiveness of influenza vaccination in previously healthy children aged from 6 months to 12 years in the 2018-2019 season.

A Case with Multiple Fungal Coinfections in a Patient who Presented with Pancoast Syndrome

Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.

Influenza Vaccine Effectiveness in Children at the Emergency Department during the 2018-2019 Season: the First Season School-aged Children Were Included in the Korean Influenza National Immunization Program

Background@#For the 2018–2019 season, the national influenza immunization program expanded to cover children aged from 6 months to 12 years in Korea. This study aimed to analyze vaccine effectiveness (VE) against influenza in children visiting the pediatric emergency room at a tertiary hospital during the 2018-2019 season. @*Methods@#Patients tested for influenza antigens from October 1st 2018 to May 31st 2019 at the pediatric emergency room of Samsung Medical Center were included. Patients' influenza antigen test results, influenza vaccination history, and underlying medical conditions were reviewed retrospectively. VE was estimated from the test-negative design study. @*Results@#Among the 2,901 visits with influenza test results 1,692 visits of 1,417 patients were included for analysis. Among these 1,417 patients, 285 (20.1%) were positive (influenza A, n = 211, 74.0%; influenza B, n = 74, 26.0%). The VE in all patients was 36.4% (95% confidence interval [CI], 13.9 to 53.1). The VE for influenza A was 37.6% (95% CI, 12.6 to 55.5) and VE for influenza B was 24.0% (−38.5 to 58.3). The VE in the age group 6 months to 12 years was significant with a value of 35.6% (95% CI, 10.5 to 53.7); it was not statistically significant in the age group 13 to 18 years. In a multivariate logistic regression model, patients who received an influenza vaccination were less likely to get influenza infection (OR, 0.6; 95% CI, 0.4 to 0.8; P = 0.001), with significant confounding factors such as age group 13 to 18 years (OR, 0.5; 95% CI, 0.3 to 0.8; P = 0.003) and underlying hematology-oncology disease (OR, 0.3;95% CI, 0.1 to 0.6; P = 0.002). @*Conclusion@#We report moderate effectiveness of influenza vaccination in previously healthy children aged from 6 months to 12 years in the 2018-2019 season.

Disseminated Septic Lesions Caused by Staphylococcus epidermidis Mimicking Cysticercosis Detected on Ultrasonography in a Pediatric Patient with Acute Myeloid Leukemia

Staphylococcus epidermidis is a part of the normal skin flora of humans. However, it can cause serious infections in people exposed to foreign bodies or in immunocompromised patients. A 13-year-old boy was hospitalized with fever and myalgia. Painful nodular lesions were detected on the scalp, arms, and legs. Pancytopenia and blasts were present in the peripheral blood. He was diagnosed with acute myeloid leukemia. Magnetic resonance imaging of the whole body showed multiple peripheral rim-enhancing, cyst-like lesions. Ultrasonography showed echogenic nodules inside the cystic lesions in the intramuscular space of the arms and legs. Therefore, cysticercosis was strongly suggested initially. However, an abscess was confirmed on sono-guided biopsy and S. epidermidis was isolated from a microbial culture of the tissue. We report a case of multiple disseminated lesions caused by S. epidermidis in a leukemia patient, initially mistaken for cysticercosis.

Analysis of the Change in Seropositive Rate of the Epstein-Barr Virus in Koreans: A Single-Center Study

Purpose@#Epstein-Barr virus (EBV) infection is related to infectious mononucleosis or nasopharyngeal cancer, and its epidemiology may change according to the socioeconomic development of communities. This study aimed to evaluate the recent epidemiology of EBV seropositive rate in Korea. @*Methods@#We retrospectively reviewed EBV serology test results obtained from a part of clinical care at Samsung Medical Center, Seoul, South Korea, from January 2000 to December 2017. @*Results@#The EBV seropositive rate in 26,527 subjects during the study period was 81.0% (21,485/26,527): 44.4% (2,716/6,122) in subjects aged 0–9 years, 75.8% (2,077/2,739) in those aged 10–19 years, and 94.5% (16,692/17,666) in those aged ≥20 years. The EBV seropositive rate decreased from 89.4% (8,592/9,616) in 2000–2008 to 76.2% (12,893/16,911) in 2009– 2017 (P<0.001). Especially, the EBV seropositive rate in subjects aged 0–19 years significantly decreased from 2000–2008 to 2009–2017 (0–9 years, 62.8% [1,172/1,866] in 2000–2008 and 36.3% [1,544/4,256] in 2009–2017; 10–19 years, 83.8% [745/858] in 2000–2008 and 70.8% (1,332/1,881) in 2009–2017) (P<0.001). @*Conclusions@#The EBV seropositive rate in children has decreased in the last 20 years. As the age of patients with primary EBV infection increased, there is a need for interest in clinical manifestation, such as infectious mononucleosis, in adolescents and young adults.

Therapeutic Drug Level Monitoring of Teicoplanin in Korean Pediatric Patients with Normal versus Impaired Renal Function

Background@#Teicoplanin is used to treat serious gram-positive infections. Optimal teicoplanin trough levels are considered to be ≥ 10 μg/mL. Despite its wide use in various clinical settings, data on teicoplanin trough level in pediatric patients are limited. Therefore, the aim of this study was to investigate the therapeutic drug level monitoring of teicoplanin in Korean pediatric patients, including those with impaired renal function. @*Methods@#A retrospective study was performed in pediatric patients (age ≤ 18 years old) who received teicoplanin from September 2014 to April 2018. The regimen included a loading dose of 10 mg/kg/dose at 12 hours' interval three times in a row, and a maintenance dose of 10 mg/kg/dose commenced at 24 hours of interval after the loading dose, with a maximum of 400 mg/dose, respectively. The first therapeutic drug levels were measured. Distribution and characteristics of trough levels in patients with decreased renal function and those with bacteremia were also assessed. @*Results@#A total of 187 trough levels were collected from 143 patients. Hematologic and oncologic diseases were the most common underlying diseases (83.2%, n = 119). One hundred eighty trough levels were first measured, and their median value was 16.2 μg/mL (range, 2.3–100 μg/mL) and the median interval between initial teicoplanin injection and 1st trough level was 96.5 hours (range 47.6–179.3 hours). Lower steady-state levels were observed in younger age group (median, 13.5 vs. 18.0 μg/mL, P = 0.038). Median trough levels were higher in patients with decreased renal functions (P < 0.001). In addition, among eight with gram-positive bacteremia, seven of them had a favorable outcome. @*Conclusion@#This study provides additive information on trough level monitoring of teicoplanin in children with impaired renal function and treatment effect in patients with gram-positive bacteremia. Careful monitoring for steady state trough levels of teicoplanin is warranted.

A contact investigation after exposure to a child with disseminated tuberculosis mimicking inflammatory bowel disease / 소아과

PURPOSE: Tuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals. METHODS: A 4-year-old child without Bacille Calmette-Guérin vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts. RESULTS: We examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB. CONCLUSION: This is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.

Characteristics and Therapeutic Outcomes of Acute Promyelocytic Leukemia in Children and Adolescents / 임상소아혈액종양

BACKGROUND: Acute promyelocytic leukemia (APL) is rare in children, accounting for 5-7% of all acute myeloid leukemia (AML) cases. This study aimed to review clinical and laboratory characteristics of pediatric APL patients, and to analyze the therapeutic outcomes. METHODS: Twenty pediatric patients with APL, diagnosed from January 1998 to April 2016, were retrospectively reviewed. Clinical and laboratory findings were collected, and morphologic, immunophenotypic, cytogenetic and molecular characteristics were evaluated. Therapeutic outcomes and prognostic factors of patients were analyzed. RESULTS: The number of pediatric APL patients was 20, which was 18.5% of all the cases of AML. The 5-year overall survival (OS) and event-free survival (EFS) were 88.5±7.6% and 83.0±9.0%, respectively. As compared to typical APL patients, patients with microgranular variants (M3v) (n=4, 20%) showed a tendency for a younger age, low white blood cell counts, and a shorter prothrombin time (P=0.045), but their 5-year OS and EFS were not significantly different. Better survival was observed in ATRA plus chemotherapy group both for 5-year OS (100% vs. 60.0±21.9%, P=0.018), and for 5-year EFS (60.0±21.9% vs. 91.7±8.0%, P=0.080) than ATRA only group. Stem cell transplantations were given to 3 patients and they are alive without disease for 8.3-16.5 years of follow-up. One death after relapse, another death in remission and development of secondary leukemia were encountered during the study period. CONCLUSION: This study analyzed clinical characteristics of pediatric APL and demonstrated very good outcome with the combination of ATRA and chemotherapy.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Genetic Rare Diseases in Children / 임상소아혈액종양

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has been established as an important curative method in genetic rare diseases in children. However, adverse effects have been obstacles for successful outcomes. This study aims to review the transplant outcomes of genetic rare diseases over the last 2 decades, to analyze the prognostic factors that may affect outcome, and to suggest future perspective of HSCT in these diseases. METHODS: Seventeen patients younger than 18 years who were transplanted at Department of Pediatrics, Chonnam National University Hospital and Chonnam National University Hwasun Hospital from 1996 to 2015 were retrospectively reviewed. Outcomes were analyzed by donor source, intensity of conditioning [myeloablative conditioning (MAC) vs. reduced-intensity conditioning (RIC)], and disease type. RESULTS: The 5-year Kaplan-Meier overall survival (OS), and event-free survival (EFS) was 64.7±14.3% and 52.9±12.9%, respectively. Among subgroups, the 5-year OS was 61.5±15.8% after RIC as compared to 28.6±17.1% after MAC (P=0.27). The 5-year EFS was 60.0±25.0% after matched sibling donor transplants, 62.5±20.4% after mismatched related/unrelated bone marrow/peripheral blood stem cell transplants, and 28.6±17.1% after unrelated umbilical cord blood transplants, respectively. The 5-year OS according to disease type was as follows: 60.0±21.9% for Fanconi anemia, 50.0±25.0% for familial hemophagocytic lymphohisticytosis. All patients with primary immunodeficiency survived, but none with adrenoleukodystrophy. CONCLUSION: Although definitive conclusions cannot be drawn due to the limited number of cases, RIC may be preferred in select, genetic rare diseases. Better strategies are required to improve outcomes after cord blood transplantation. Moreover, special attention should be given to minimize late complications in children.

Outcomes of Hematopoietic Stem Cell Transplantation by Donor Types in Children with Acute Myeloid Leukemia / 임상소아혈액종양

BACKGROUND: The aim of this study was to compare the outcomes of children with acute myeloid leukemia (AML) who received stem cell transplantation from different donor groups. METHODS: This study included 37 pediatric AML patients who received allogeneic stem cell transplantation from March 1996 to December 2012 at Chonnam National University Hospital and Chonnam National University Hwasun Hospital. The overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GvHD), relapse and transplant-related mortality (TRM) were compared between different donor groups. RESULTS: Transplant donor groups included matched sibling donor (MSD, n=15), unrelated donor (URD=13), unrelated umbilical cord blood (UCB, n=7), or haploidentical donor (HD, n=2). Twenty-six patients survived with a median follow-up of 7.3 years. The 7-year EFS rates were 80.0±10.3% in MSD, 69.2±12.8% in URD and 57.1±18.7% in UCB, and 0% in HD, respectively (P=0.019). The CI of relapse at 5 years was 20.0%, 15.4%, 33.3%, 50%, respectively (P=0.721). The CI of TRM at 2 years was 0%, 15.4%, 16.7%, 50.0%, respectively in each donor group (P=0.017). The CI of grade II-IV acute and extensive chronic GvHD were higher in UCB (P=0.003, P=0.020, respectively). There were no significant differences in OS, EFS, and CI of TRM and relapse between allele-mismatched URD and UCB. CONCLUSION: Despite the limitation of small number of patients, the comparable outcome of pediatric AML patients transplanted from alternative donor with those transplanted from MSD are encouraging. Especially, if a matched donor is not available, allele-mismatched URD or UCB transplant may offer the advantage of prompt availability for patients who urgently require transplantation.

Characteristics and Therapeutic Outcomes of Acute Promyelocytic Leukemia in Children and Adolescents / 임상소아혈액종양

BACKGROUND: Acute promyelocytic leukemia (APL) is rare in children, accounting for 5-7% of all acute myeloid leukemia (AML) cases. This study aimed to review clinical and laboratory characteristics of pediatric APL patients, and to analyze the therapeutic outcomes.METHODS: Twenty pediatric patients with APL, diagnosed from January 1998 to April 2016, were retrospectively reviewed. Clinical and laboratory findings were collected, and morphologic, immunophenotypic, cytogenetic and molecular characteristics were evaluated. Therapeutic outcomes and prognostic factors of patients were analyzed.RESULTS: The number of pediatric APL patients was 20, which was 18.5% of all the cases of AML. The 5-year overall survival (OS) and event-free survival (EFS) were 88.5±7.6% and 83.0±9.0%, respectively. As compared to typical APL patients, patients with microgranular variants (M3v) (n=4, 20%) showed a tendency for a younger age, low white blood cell counts, and a shorter prothrombin time (P=0.045), but their 5-year OS and EFS were not significantly different. Better survival was observed in ATRA plus chemotherapy group both for 5-year OS (100% vs. 60.0±21.9%, P=0.018), and for 5-year EFS (60.0±21.9% vs. 91.7±8.0%, P=0.080) than ATRA only group. Stem cell transplantations were given to 3 patients and they are alive without disease for 8.3-16.5 years of follow-up. One death after relapse, another death in remission and development of secondary leukemia were encountered during the study period.CONCLUSION: This study analyzed clinical characteristics of pediatric APL and demonstrated very good outcome with the combination of ATRA and chemotherapy.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Genetic Rare Diseases in Children / 임상소아혈액종양

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has been established as an important curative method in genetic rare diseases in children. However, adverse effects have been obstacles for successful outcomes. This study aims to review the transplant outcomes of genetic rare diseases over the last 2 decades, to analyze the prognostic factors that may affect outcome, and to suggest future perspective of HSCT in these diseases.METHODS: Seventeen patients younger than 18 years who were transplanted at Department of Pediatrics, Chonnam National University Hospital and Chonnam National University Hwasun Hospital from 1996 to 2015 were retrospectively reviewed. Outcomes were analyzed by donor source, intensity of conditioning [myeloablative conditioning (MAC) vs. reduced-intensity conditioning (RIC)], and disease type.RESULTS: The 5-year Kaplan-Meier overall survival (OS), and event-free survival (EFS) was 64.7±14.3% and 52.9±12.9%, respectively. Among subgroups, the 5-year OS was 61.5±15.8% after RIC as compared to 28.6±17.1% after MAC (P=0.27). The 5-year EFS was 60.0±25.0% after matched sibling donor transplants, 62.5±20.4% after mismatched related/unrelated bone marrow/peripheral blood stem cell transplants, and 28.6±17.1% after unrelated umbilical cord blood transplants, respectively. The 5-year OS according to disease type was as follows: 60.0±21.9% for Fanconi anemia, 50.0±25.0% for familial hemophagocytic lymphohisticytosis. All patients with primary immunodeficiency survived, but none with adrenoleukodystrophy.CONCLUSION: Although definitive conclusions cannot be drawn due to the limited number of cases, RIC may be preferred in select, genetic rare diseases. Better strategies are required to improve outcomes after cord blood transplantation. Moreover, special attention should be given to minimize late complications in children.

Outcomes of Hematopoietic Stem Cell Transplantation by Donor Types in Children with Acute Myeloid Leukemia / 임상소아혈액종양

BACKGROUND: The aim of this study was to compare the outcomes of children with acute myeloid leukemia (AML) who received stem cell transplantation from different donor groups.METHODS: This study included 37 pediatric AML patients who received allogeneic stem cell transplantation from March 1996 to December 2012 at Chonnam National University Hospital and Chonnam National University Hwasun Hospital. The overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GvHD), relapse and transplant-related mortality (TRM) were compared between different donor groups.RESULTS: Transplant donor groups included matched sibling donor (MSD, n=15), unrelated donor (URD=13), unrelated umbilical cord blood (UCB, n=7), or haploidentical donor (HD, n=2). Twenty-six patients survived with a median follow-up of 7.3 years. The 7-year EFS rates were 80.0±10.3% in MSD, 69.2±12.8% in URD and 57.1±18.7% in UCB, and 0% in HD, respectively (P=0.019). The CI of relapse at 5 years was 20.0%, 15.4%, 33.3%, 50%, respectively (P=0.721). The CI of TRM at 2 years was 0%, 15.4%, 16.7%, 50.0%, respectively in each donor group (P=0.017). The CI of grade II-IV acute and extensive chronic GvHD were higher in UCB (P=0.003, P=0.020, respectively). There were no significant differences in OS, EFS, and CI of TRM and relapse between allele-mismatched URD and UCB.CONCLUSION: Despite the limitation of small number of patients, the comparable outcome of pediatric AML patients transplanted from alternative donor with those transplanted from MSD are encouraging. Especially, if a matched donor is not available, allele-mismatched URD or UCB transplant may offer the advantage of prompt availability for patients who urgently require transplantation.

Changes in Birth Rate, Perinatal Risk Factors and Outcome in Newborns in Multi-cultural Family: Ten-year Experience in One Center

PURPOSE: The aim of this study is to investigate the periodical changes of birth rate, perinatal risk factors and outcome of newborns in multi-cultural families with Korean male and non-Korean, Asian female in Gwangju, Chonnnam province. METHODS: We enrolled newborns born in or transferred from other hospital to Chonnam National University Hospital between January 2001 and December 2010. They were categorized into two periods: data from 2001 to 2005 was defined as period I and from 2006 to 2010 was defined as period II. The clinical data of the birth rate, perinatal risk factors and outcome were retrospectively reviewed. RESULTS: Number and rate of newborns in multicultural families increased significantly. The nationality of the mother changed: Vietnamese, Chinese and Cambodian significantly increased; and Japanese and Filipino significantly decreased. As the maternal age tended to be younger in period II, the age gap between the spouses increased, and the paternal age significantly increased, especially in age group of over 45 year-old. Among other perinatal risk factors, premature rupture of membranes and oligohydramnios were decreased. There were no statistical difference in morbidity (except hyperbilirubinemia) and mortality. However, congenital anomalies significantly increased. CONCLUSION: As the number of newborns in multicultural families has increased, the incidence of congenital anomalies also increased. We carefully presumed this result could be caused by increasing paternal age. Careful concern and management are needed for these families and further prospective studies are needed in a larger number of subjects.

Usefulness of Serum Alkaline Phosphatase in Predicting Osteopenia and Rickets in Very Low Birth Weight Infants

PURPOSE: This study assesses the usefulness of alkaline phosphatase (ALP) in predicting the radiologic osteopenia and rickets for very low birth weight infants (VLBWI) below 1,500 g of birth weight. METHODS: Medical records of 258 VLBWI who were admitted at NICU between January 2009 and December 2011 were reviewed retrospectively. ALP max was defined by maximum level of ALP during admission. Subjects were divided into two groups: the study (n=112, ALP max > or =450 IU/L) and the control group (n=146, ALP max <450 IU/L). The two groups were compared based on the demographic and perinatal risk factors, clinical parameters, and morbidity. Also compared between the groups were: the level of ALP max, total and ionized calcium, inorganic phosphorus, and radiologic finding. To assess the usefulness of ALP in predicting the radiologic osteopenia and rickets, the sensitivity, specificity, and the positive (PPV) and negative predictive values (NPV) according to ALP max level were examined. A receiver operator characteristic (ROC) curve was constructed to determine the optimal cut-off value of ALP for the radiologic diagnosis. RESULTS: The study group was more immature and smaller, and had more perinatal risk factors with higher morbidity. The sensitivity and specificity for the radiologic finding on the basis of ALP max 450 IU/L were 68.8% and 64.9%, PPV 39.3%, and NPV 86.3% with a significance (P<0.001). In ROC curve, we observed the appropriate cut-off value to be 459.5 IU/L (P<0.001). CONCLUSION: The baseline of ALP max 450 IU/L was useful in predicting the radiologic osteopenia and rickets in VLBWI.

Two Cases of Hallermann-Streiff Syndrome Diagnosed in Early Neonatal Period

Hallermann-Streiff syndrome is a very rare congenital disorder, which is primarily characterized by the head and face abnormalities. Approximately 180 cases have been reported worldwide, including 8 cases in Korea since it was first described by Hallermann in 1893. Patients exhibit a bird-like face, hypotrichosis, atrophy of skin, dental abnormalities, proportionate nanism, and various ophthalmic disorders, including congenital cataracts and bilateral micropthalmia. As a result of many life-threatening complications, such as respiratory and cardiac difficulties, many patients die during infancy. We report here two cases of HSS diagnosed immediately after birth with literature reviews. They showed two additional characteristics, including chubby cheeks and antenatal ultrasonographic findings, which have not been mentioned in previous reports.