Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. @*Materials and Methods@#Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. @*Results@#Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). @*Conclusion@#This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

A Multi-Center Educational Research Regarding Breastfeeding for Pediatrics Residents in Korea

Purpose@#Pediatricians have a significant responsibility to educate mothers about the importance of breastfeeding. However, there have been minimal efforts in the courses of resident training in Korea. The purpose of this study is to evaluate the change in knowledge and attitude before and after a 4-week breastfeeding educational intervention among multicenter residents. @*Methods@#Prospective interventional educational research was designed for residents at eight training hospitals in Korea. Institutional reviews were obtained in each hospital. The education curriculum consisted of 14 courses regarding breastfeeding theory and practice. These materials were used to teach pediatric residents for 4 weeks. Knowledge-based tests were administered before the course, and re-tests were administered after the course using different test items of similar levels. Test scores and survey responses were compared before and after the intervention. @*Results@#A total of 73 residents (1st year 20, 2nd year 23, 3rd year 16, and 4th year residents 14) from eight training hospitals completed the intervention. Their average age was 30.3±2.9 years, 17 (23.3%) were male, 22 (30.1%) were married, and eight had more than one child of their own. The mean pre-test score was 61.8±13.4 and the mean post-test score was 78.3±7.5 (P<0.001). The inter-grade difference in the score was significant in the pre-test (P=0.005), but not significant in the post-test (P=0.155). There were more responses of obtaining confidence after the intervention (P<0.001). @*Conclusion@#In our study, pediatric residents showed improvement in their knowledge and confidence level after 4 weeks of the breastfeeding curriculum. This will provide a basis for future policymaking in the training of pediatric residents regarding breastfeeding in Korea.

Significance of Evaluation for von Willebrand Disease in Premenopausal Women with Iron Deficiency Anemia and Menorrhagia / 임상소아혈액종양

Background@#In Korea, in the case of patients with significant bleeding symptoms due to unknown causes, there are very few studies that evaluate bleeding disorders, including von Willebrand disease (VWD ). VWD should be considered as an important causative factor in patients with iron deficiency anemia (IDA) and unexplained menorrhagia. This study aimed to understand the clinical characteristics of VWD and the significance of evaluation for VWD in premenopausal women in Korea with menorrhagia and ID A. @*Methods@#Premenopausal women who were diagnosed with IDA and menorrhagia from January 2009 to March 2020 were included. IDA was diagnosed by either low ferritin or transferrin saturation with microcytic anemia. Menorrhagia was evaluated based on the medical records obtained from a gynecologist. VWD diagnosis was defined as von Willebrand factor antigen ＜50% and von Willebrand factor ristocetin cofactor activity ＜50%, which were low according to the Hospital for Sick Children criteria. @*Results@#Out of a total of 120 patients, only 12 were tested for VWD, all of whom were pediatric patients. Four of the 12 pediatric patients tested were diagnosed with VWD and 4 of the 120 (3.3%) patients with IDA and menorrhagia were diagnosed with VWD. Three out of the 4 patients was diagnosed with VWD by repeat screening test. Although all parameters are not statistically significant, VWD patients tended to have ID A at a younger age (13.25 vs. 15.00 years) and were more likely to have recurrent IDA than patients without VWD. @*Conclusion@#Clinical doctors should consider VWD if patients have menorrhagia with ID A. If VWD is suspected, repeated VWD screening tests are necessary to increase the diagnosis rate. Accurate diagnosis of VWD in patients with significant bleeding may facilitate decisions for appropriate treatment.

Significance of Evaluation for von Willebrand Disease in Premenopausal Women with Iron Deficiency Anemia and Menorrhagia / 임상소아혈액종양

Background@#In Korea, in the case of patients with significant bleeding symptoms due to unknown causes, there are very few studies that evaluate bleeding disorders, including von Willebrand disease (VWD ). VWD should be considered as an important causative factor in patients with iron deficiency anemia (IDA) and unexplained menorrhagia. This study aimed to understand the clinical characteristics of VWD and the significance of evaluation for VWD in premenopausal women in Korea with menorrhagia and ID A. @*Methods@#Premenopausal women who were diagnosed with IDA and menorrhagia from January 2009 to March 2020 were included. IDA was diagnosed by either low ferritin or transferrin saturation with microcytic anemia. Menorrhagia was evaluated based on the medical records obtained from a gynecologist. VWD diagnosis was defined as von Willebrand factor antigen ＜50% and von Willebrand factor ristocetin cofactor activity ＜50%, which were low according to the Hospital for Sick Children criteria. @*Results@#Out of a total of 120 patients, only 12 were tested for VWD, all of whom were pediatric patients. Four of the 12 pediatric patients tested were diagnosed with VWD and 4 of the 120 (3.3%) patients with IDA and menorrhagia were diagnosed with VWD. Three out of the 4 patients was diagnosed with VWD by repeat screening test. Although all parameters are not statistically significant, VWD patients tended to have ID A at a younger age (13.25 vs. 15.00 years) and were more likely to have recurrent IDA than patients without VWD. @*Conclusion@#Clinical doctors should consider VWD if patients have menorrhagia with ID A. If VWD is suspected, repeated VWD screening tests are necessary to increase the diagnosis rate. Accurate diagnosis of VWD in patients with significant bleeding may facilitate decisions for appropriate treatment.

A Case of Adrenal Myelolipoma Associated with Hereditary Spherocytosis / 임상소아혈액종양

Hereditary spherocytosis is the most common hereditary red blood cell membrane disorder. It results from a deficiency in certain proteins that are part of the red blood cell membrane cytoskeleton. We report a case of adrenal myelolipoma in a 23-yearold patient with hereditary spherocytosis. She was diagnosed with hereditary spherocytosis at 7 months of age. As she grew older, hemoglobin level was low, so splenectomy was recommended, but continuous follow up was not possible due to the circumstances of the patient, so the splenectomy was delayed. Adrenal myelolipoma was discovered incidentally at the age of 23 with abdominal pain and cholecystitis with gallstones at the time. Myelolipoma is a benign tumor of the mesenchymal origin;its etiology remains unclear. Myelolipoma is composed of adipose and hematopoietic tissues and mainly arises from adrenal tissues. The mass is often detected during routine radiologic examinations because myelolipoma is usually asymptomatic and not generally associated with hematologic diseases. The prevalence of myelolipoma appears to be increasing due to the increased use of imaging modalities. The association of myelolipoma with hereditary spherocytosis has rarely been reported in the literature. To our best knowledge, this is the first report of adrenal myelolipoma associated with hereditary spherocytosis in the Korean population.

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.

A Multicenter Study on von Willebrand Disease Realities in Yeungnam Region / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.

A Case of Solitary Rectal Ulcer Syndrome in a 16-year-old Girl Presented with Iron Deficiency Anemia / 임상소아혈액종양

Solitary rectal ulcer syndrome (SRUS) is a rare condition that is most commonly characterized by rectal pain and bleeding. It can be accompanied by diarrhea or constipation, tenesmus, and rectal prolapse. Considering its non-specific symptoms, it is often difficult to diagnose, particularly in children. The underlying etiology of SRUS is not fully understood; however, it may be secondary to ischemic changes in the rectum associated with paradoxical contraction of the pelvic floor and external anal sphincter muscles and rectal prolapse. The macroscopic appearance of the rectal lesion may vary from hyperemia to ulceration or a polypoid lesion that can mimic carcinoma, although the histological findings are characteristic, with fibromuscular obliteration of the lamina propria and disorientation of muscle fibers. We report an adolescent case of SRUS developed in a 16-year-old adolescent girl who presented with iron deficiency anemia.

Diffuse Neonatal Hemangiomatosis with Unilateral Cranial Nerve Palsy Improved by Propranolol

Diffuse neonatal hemangiomatosis (DNH) is characterized by multiple capillary or cavernous hemangiomas on the skin and internal organs occurring during the neonatal period. It is a life-threatening condition due to high-output heart failure with a mortality rate of 60-85% without proper treatment. The areas that are most commonly involved include the skin (100%), liver (64-100%), and central nervous system (52%). Corticosteroids are the drugs of choice as an initial treatment and have a response rate of 30-60%. We present here a case of a newborn baby with multiple hemangiomas on her skin (scalp, lips, neck, back, shoulder, arm, buttock, and leg), brain (right cerebellum, pons, and medulla oblongata), lungs, liver, kidney, and bones. She suffered from 6th, 7th, 9th, 10th, and 12th cranial nerve palsy resulting from hemorrhage of the hemangiomas in the brain. The first-line treatment of prednisolone (4 mg/kg/day) was not effective and propranolol (2 mg/kg/day) was administered as a second-line treatment. After 2 weeks of treatment, the hemangiomas had decreased in size with no associated acute hemorrhage. The infant is now 10 months old and both the multiple hemangiomas and cranial nerve palsy have improved. Propranolol was effective without significant adverse effects in treating DNH resistant to corticosteroids.

A Case of Solitary Rectal Ulcer Syndrome in a 16-year-old Girl Presented with Iron Deficiency Anemia / 임상소아혈액종양

Solitary rectal ulcer syndrome (SRUS) is a rare condition that is most commonly characterized by rectal pain and bleeding. It can be accompanied by diarrhea or constipation, tenesmus, and rectal prolapse. Considering its non-specific symptoms, it is often difficult to diagnose, particularly in children. The underlying etiology of SRUS is not fully understood; however, it may be secondary to ischemic changes in the rectum associated with paradoxical contraction of the pelvic floor and external anal sphincter muscles and rectal prolapse. The macroscopic appearance of the rectal lesion may vary from hyperemia to ulceration or a polypoid lesion that can mimic carcinoma, although the histological findings are characteristic, with fibromuscular obliteration of the lamina propria and disorientation of muscle fibers. We report an adolescent case of SRUS developed in a 16-year-old adolescent girl who presented with iron deficiency anemia.

Two Cases of Infant Hemophilia A Patients with Inhibitors / 임상소아혈액종양

Development of inhibitors is currently one of the most serious complications of hemophilia treatment. Typically, the propensity to develop an inhibitor is likely influenced by both genetic and non-genetic factors. Hemophilia patients with inhibitors are partially or completely refractory to traditional replacement of the deficient clotting factors and are at increased risk of bleeding as compared to patients without inhibitors. Several cases of infant hemophilia A with inhibitor have been reported in other countries, but no such patient has so far been reported in South Korea. We report two infants affected by hemophilia A with inhibitors, both of whom had bleeding episodes that were successfully treated with recombinant activated factor VII. Clinicians should remain aware of potential inhibitor development in infant hemophilia A patients and such patients should be carefully monitored.

Two Cases of Infant Hemophilia A Patients with Inhibitors / 임상소아혈액종양

Development of inhibitors is currently one of the most serious complications of hemophilia treatment. Typically, the propensity to develop an inhibitor is likely influenced by both genetic and non-genetic factors. Hemophilia patients with inhibitors are partially or completely refractory to traditional replacement of the deficient clotting factors and are at increased risk of bleeding as compared to patients without inhibitors. Several cases of infant hemophilia A with inhibitor have been reported in other countries, but no such patient has so far been reported in South Korea. We report two infants affected by hemophilia A with inhibitors, both of whom had bleeding episodes that were successfully treated with recombinant activated factor VII. Clinicians should remain aware of potential inhibitor development in infant hemophilia A patients and such patients should be carefully monitored.

A Adrenocortical Oncocytoma in a 10-year-old Girl Presenting with Virilization / 임상소아혈액종양

Adrenocortical oncocytoma is a rare epithelial tumor only described in adults and in most cases, benign and non-functioning. Histologically characterized by cells with eosinophilic granular cytoplasm and ultra-structurally by the presence of numerous closely packed mitochondria. We report a case of adrenal oncocytoma developed in a 10-year-old girl who presented a left adrenal mass with low voice tone, excessive hair growth, and elevation of the plasma testosterone and dehydroepiandrosterone sulfate levels as a result of overproduction of adrenal steroid hormones. After the left adrenalectomy, her hormone levels were normalized.

A Adrenocortical Oncocytoma in a 10-year-old Girl Presenting with Virilization / 임상소아혈액종양

Adrenocortical oncocytoma is a rare epithelial tumor only described in adults and in most cases, benign and non-functioning. Histologically characterized by cells with eosinophilic granular cytoplasm and ultra-structurally by the presence of numerous closely packed mitochondria. We report a case of adrenal oncocytoma developed in a 10-year-old girl who presented a left adrenal mass with low voice tone, excessive hair growth, and elevation of the plasma testosterone and dehydroepiandrosterone sulfate levels as a result of overproduction of adrenal steroid hormones. After the left adrenalectomy, her hormone levels were normalized.

CMV antigenemia following pediatric hematopoietic stem cell transplantation:risk factors and outcomes / 소아과

PURPOSE: Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided pre-emptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. METHODS: We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. RESULTS: CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade > or=II) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade > or=II) were the independent risk factors for positive CMV antigenemia. CONCLUSION: Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

Short-term follow up of thyroid function after pediatric hematopoietic stem cell transplantation / 소아과

PURPOSE: In this study, we analyzed the short term changes of thyroid function, incidence and risk factors of thyroid dysfunction soon after allogeneic hematopoietic stem cell transplantation (HSCT) in children. METHODS: We enrolled 80 pediatric patients following allogeneic HSCT, at the Catholic HSCT center between January, 2004 and February, 2006. Serum TSH (thyroid stimulating hormone), total serum thyroxine and total serum triiodothyronine levels were systematically measured in 80 patients before the HSCT, and at 1 month, 6 months and 12 months after HSCT. RESULTS: Thyroid function statistically decreased at 1 month after HSCT(P or = II) were risk factors for ETS (P=0.04, 0.01 respectively). In multivariate analysis, we could not detect an independent risk factor for ETS (P=0.19, 0.06 respectively). CONCLUSION: The present study suggests that the incidence of thyroid dysfunction is high after allogeneic HSCT. Therefore, regular monitoring of thyroid hormone levels after HSCT is required.

Isolated Thymic Langerhans Cell Histiocytosis / 대한소아혈액종양학회지

Langerhans cell histiocytosis is a rare disease in which the Langerhans cells proliferate abnormally, like a cancer, and involve various tissues and organs, such as skin, bone, lung, lymph node, liver and spleen. Especially, in the younger age, it usually involves more organs and tissues, sometimes including the thymus. But isolated involvement of thymus is very rare. We report an 11-month-old-girl with an isolated thymic involvement of Langerhans cell histiocytosis with a brief review of related literatures.

Acute Myeloid Leukemia after Chemotherapy for Osteosarcoma: A Case Report / 대한소아혈액종양학회지

There have been advances for the treatment of childhood cancers since the recent several decades, which caused increased incidence of secondary malignancy in the populations of the long term survivors from the primary cancers. The authors report a case of acute myeloid leukemia as a secondary malignancy in a 19-year-old female after successful chemotherapy for osteosarcoma, with a brief review of related literatures.

Angiotensinogen M235T Polymorphism in Children with Henoch-Schonlein Purpura Nephritis

PURPOSE: Henoch-Schonlein purpura(HSP) nephritis has a variable range of prevalence from 25 to 50% among HSP patients and is a common cause of chronic glomerulonephritis in children. In our study, we evaluated the distribution and the association of the angiotensinogen(AGT) M235T polymorphism with the clinical manifestations, particularly proteinuria in children with HSP with or without nephritis. METHODS: The AGT M235T polymorphism was determined in children with HSP nephritis (n=33) or HSP without nephritis(n=28) who had been diagnosed at Busan Paik hospital from January 1996 to June 2001. The M235T polymorphism of the AGT gene was determined by PCR amplification of the genomic DNA. RESULTS: The M235T polymorphism of AGT gene frequency was MM:75%, MT:25%, TT:0% in HSP and MM:64%, MT:36%, TT:0% in HSP nephritis, there was no significant differences in the genotype and allele frequencies between the two groups. No significant differences in clinical manifestations at onset and last follow-up were seen between the two genotypes. When statistical analysis was done according to the presence of the M allele, the amount of 24-hour urinary protein excretion and the incidence of moderate to heavy proteinuria(>500 mg/m2/day) at onset and at last follow-up were higher in the MT genotype than in those of in the MM genotype but these difference were not statistically significant. CONCLUSION: We suggest a lack of association between M235T polymorphism of the AGT gene and clinical manifestations in children with HSP nephritis. However, further follow-up studies based on sufficient number of patients and long term follow up periods are necessary to confirm the role of M235T polymorphism of AGT gene in children with HSP nephritis.

Neuron-Specific Enolase Levels of Serum and Cerebrospinal Fluid in Children with Febrile Seizure

PURPOSE: Neuron-specific enolase(NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizure cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE. METHODS: Twenty-one pateints were enrolled. The maximal seizure duration was 90 mins. Blood and CSF samples for the measurement of NSE were obtained immediately after the seizure. NSE was measured using an immunoradiometric assay(IRMA). RESULTS: The CSF NSE level of the febrile seizure group was 11.7+/-2.04 ng/mL and that of the control group was 11.3+/-5.7 ng/mL. The serum NSE level of the febrile seizure group was higher than the serum NSE level of the control group, but there was no significant correlation. The serum NSE level of the febrile seizure group was 19.0+/-7.5 ng/mL and that of the control group was 12.8+/-5.1 ng/mL. The serum NSE level of the febrile seizure group was significantly higher than the serum NSE level of the control group. The CSF/serum ratio of NSE in the febrile seizure group was 0.7+/-0.3 and that of the control group was 1.0+/-0.5. The CSF/serum ratio of NSE in the febrile seizure group was lower than the CSF/serum ratio of NSE in the control group and there was a significant correlation. There was no significant correlation between seizure duration, serum NSE, CSF NSE, and the ratio of the CSF to the serum level of NSE. CONCLUSION: Children with febrile seizure are at relatively low risk for neuronal damage following seizures.