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Background Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre‐treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration‐Hepatoblastoma Stratification (CHIC‐HS) system, with survival outcomes. Methods We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. Results The 5‐year overall survival (OS), event‐free survival (EFS), and transplant‐free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P, Survival rates were significantly improved among children with hepatoblastoma, especially those with advanced PRETEXT stages with positive annotation factors due to advances in surgical techniques and the introduction of effective chemotherapy. Prognostic factors had different clinical implications with evolved treatment modalities.

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

Background B‐ and T‐lymphocyte attenuator (BTLA) and programmed cell death‐1 (PD‐1) inhibit γδ T cell homeostasis and activation. This study aimed to determine whether BTLA and PD‐1 signaling pathways were convergent or independent in human peripheral blood γδ T cells. Herein we demonstrate that the signalings of BTLA and PD‐1 regulated proliferation and cytotoxicity of human γδ T cells, respectively. Methods Human peripheral blood γδ T cells were cultured with inactivated Jurkat cells in the presence of interleukin‐2 and zoledronate (Zol) for 14 days. Flow cytometry was performed to evaluate the phenotypes and functions of γδ T cells. Results The proliferation of the γδ T cells was increased when PBMCs were cocultured with inactivated herpes virus entry mediator (HVEM)low Jurkat cells. The cytotoxicity of the expanded γδ T cells was not affected by coculture with inactivated HVEMlow Jurkat cells and was further increased in the presence of anti‐PD‐L1 mAb. These results suggest that the inactivation of the BTLA signaling pathway during expansion could help produce more γδ T cells without compromising γδ T cell function. The inhibition of BTLA or PD‐1 signaling repressed phosphorylation of the src homology region 2‐containing protein tyrosine phosphatase 2 and increased the phosphorylation of protein kinase B in γδ T cells. However, there were no synergistic or additive effects by a combination of BTLA and PD‐1 blockade. Conclusion These results suggest that BTLA signaling is crucial in regulating γδ T cell proliferation and function and that the BTLA and PD‐1 signaling pathways act independently on the proliferation and cytotoxicity of human peripheral γδ T cells., Blocking B‐ and T‐lymphocyte attenuator (BTLA) signaling increases γδ T cell proliferation ex vivo. BTLA signaling regulates γδ T cell proliferation and programmed cell death‐1 regulates effector function without affecting the other.

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

Hepatoblastoma is the most common malignant hepatic tumor in infants and young children and accounts for approximately 1% of all pediatric malignancies. A treatment strategy incorporating chemotherapy and surgical resection has evolved based on the results of the multicenter clinical trials performed by the major liver study groups during the last two decades and led to significantly improved survival outcomes. The alpha-fetoprotein level, PRE-Treatment EXTent tumor stage, and histological category are well-known prognostic factors that are used for risk stratification. Platinum-based chemotherapy regimens are effective in terms of increasing the likelihood of surgical resectability. Refinement of surgical techniques and the advent of liver transplantation have improved the outcomes in patients with advanced tumors. However, the optimal treatment strategy for advanced hepatoblastoma remains unclear. Unanswered questions include the optimal timing and indications for pulmonary metastasectomy and when the surgical strategy should be complex liver resection or liver transplantation. The major liver study groups have now formed a global coalition known as the Children’s Hepatic tumors International Collaboration and developed an international staging system. The aim of this article is to review current treatment strategies of hepatoblastoma focusing on high risk patients.

The incorporation of a reduced-intensity conditioning (RIC) regimen in hematopoietic cell transplantation (HCT) for patients with hemophagocytic lymphohistiocytosis (HLH) has decreased early mortality but is associated with a high rate of mixed chimerism and graft failure. Here, we present a successful single-center experience using busulfan and a fludarabine-based RIC regimen for the treatment of HLH.The medical records of pediatric patients with HLH who underwent HCT using a busulfan/ fludarabine-based RIC regimen between January 2008 and December 2017 were reviewed retrospectively.Nine patients received HCT with a busulfan/fludarabine-based RIC regimen. Three patients had primary HLH, and the other six patients had secondary HLH with multiple reactivations. All three patients with primary HLH hadOur experience suggests that a busulfan/fludarabine-based RIC regimen is a viable option for pediatric patients with HLH who require HCT.

Simple Summary Neurologic complications following a hematopoietic stem cell transplantation (HSCT) can be caused by various etiologies and significantly contribute to morbidity and mortality. The aim of our retrospective study was to determine the prognostic indicators for HSCT-associated neurological complications in pediatric HSCT recipients using their clinical characteristics and brain magnetic resonance imaging (MRI) lesions. The demographics, received treatments, treatment-related morbidities, laboratory findings and brain MRI findings were reviewed and compared among 51 patients who had underwent a brain MRI due to newly developed neurological symptoms or infection signs during HSCT and follow-up period. Children with neurologic complications associated with infectious causes, malignant disease or severe brain MRI abnormalities were more likely to have poor outcome. Abstract Purpose: To determine the prognostic indicators for hematopoietic stem cell transplantation (HSCT)-associated neurological complications, the clinical characteristics and brain magnetic resonance imaging (MRI) lesions in pediatric HSCT recipients were reviewed. Methods: This retrospective study included 51 patients who had underwent a brain MRI due to newly developed neurological symptoms or infection signs during chemotherapy or HSCT. We reviewed the demographics, received treatments, treatment-related morbidities, laboratory findings and brain MRI findings, which were compared between good and poor neurologic outcome groups. Results: Thirty-seven patients (72.5%) fully recovered from the neurologic deficits and fourteen (27.5%) persisted or aggravated. The children with an underlying malignant disease had significantly poorer neurological outcomes (p = 0.015). The neurologic complications associated with infection were more frequent in the poor outcome group (p = 0.038). In the neuroimaging findings, the extent of the white matter lesions was significantly higher in the poor outcome group, as was that of abnormal enhancement, ventriculomegaly, cortical change, deep gray matter abnormalities and cerebellar abnormalities. Conclusion: Most children with neurologic complications and neuroimaging abnormalities during HSCT had recovered. However, children with neurologic complications associated with infectious causes, malignant disease or severe brain MRI abnormalities should be more carefully monitored during HSCT.

Background Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders (EBV-T/NK-LPD) is a group of rare disorders resulting from EBV-infected T/NK-cells. It manifests as a broad spectrum of clinical symptoms according to immunologic status and viral load of an infected patient. Here, we report a boy who developed central nervous system (CNS) vasculitis and myelopathy as possible neurologic manifestations of EBV-T/NK-LPD. Case report A 16-year-old boy came to our hospital with a necrotic skin lesion on his right shoulder. He suffered from local skin reactions with high fevers after mosquito bites since he was 10 years old. During the evaluation of his skin lesion, he suddenly developed left facial palsy. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) showed acute infarctions of the pons and middle cerebellar peduncle and irregularities of both anterior inferior cerebellar arteries. Serologic testing showed an elevation of total Ig E levels, anti-VCA IgG levels, and anti-EA IgG titers. EBV DNA copy numbers of the whole blood and cerebrospinal fluid (CSF) were elevated. Biopsy of the right shoulder skin showed extranodal NK/T-cell lymphoma. According to clinical features and laboratory findings, he was diagnosed with EBV-T/NK-LPD. He was treated with chemotherapy and hematopoietic stem cell transplantation but developed recurrent infarctions during treatment. Conclusion This case showed the diagnostic challenge of neurologic manifestations of EBV-T/NK-LPD. EBV-T/NK-LPD-associated CNS vasculitis needs to be considered as a differential diagnosis of CNS vasculitis, when it is accompanied by the typical clinical spectrum of EBV-T/NK-LPD such as severe mosquito bite allergy, extranodal NK/T-cell lymphoma.

PurposeThe presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia.Materials and MethodsMedical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed.ResultsFive hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases at diagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphoma were 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL) were 71% and 56% (p < 0.001). Central nervous system involvement, high lactate dehydrogenase level (> 250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (p < 0.001).ConclusionIn East Asia, PTCL was more frequent than in Western countries, and bone marrow involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

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., Graphical Abstract

Natural killer (NK)/T-cell lymphoma is an aggressive malignancy [1]. Although regimens including asparaginases are effective and increase the complete remission rate [2], the outcomes for stage IV ...

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using

We aimed to evaluate treatment outcomes of pediatric acute lymphoblastic leukemia (ALL) subgroups by risk-stratification, in the Yeungnam region of Korea.We reviewed the courses of 409 newly diagnosed ALL patients from January 2004 to December 2013 in the Yeungnam region.All patients were classified into three risk groups: standard risk (SR, n=212), high risk (HR, n=153) and very high risk (VHR, n=44). The mean follow-up time was 73.6 ± 39.4 months. The 7-year event-free survival (EFS) and overall survival (OS) rates were 78.7 ± 2.1% and 86.8 ± 1.8%, respectively. Significant 7-year EFS and OS rates for SR (84.0 ± 2.7%, 93.7 ± 1.8%), HR (76.5 ± 3.5%, 82.1 ± 3.3%), and VHR (60.6 ± 7.5%, 69.9 ± 7.5%) were observed (P0.001), respectively. Relapse occurred in 52 patients, and the cumulative 7-year incidence of relapse differed according to risk groups (SR vs. HR vs. VHR=12.6% vs. 14.0% vs. 29.6%, P=0.003).For the 46 relapsed patients who were treated, the 3-year EFS and OS were 42.3 ± 8.3%and 46.4± 8.4%. Among the 44 VHR patients, EFS was not significantly different between the chemotherapy-treated patients and those received hematopoietic stem cell transplantation (P=0.533). The 7-year EFS of the hyperleukocytosis subgroup (24 cases, 14 under 10 years of age)showed a tendency for better prognosis than that of the other VHR subgroups (P=0.178).Our results revealed improved outcomes in pediatric ALL patients with risk-stratified therapy. The hyperleukocytosis subgroup without any combined chromosomal abnormalities may respond favorably to chemotherapy alone after first complete remission.

Purpose Hematopoietic Stem Cell Transplantation (HSCT) is the only curative treatment for patients with familial, relapsing, or persistent hemophagocytic lymphohistiocytosis (HLH). Here, we present a single center experience of using busulfan (Bu) and fludarabine (Flu) based reduced intensity conditioning regimen (RIC) for treatment of HLH. Methods Medical records of pediatric patients with HLH, who received HSCT using Bu/Flu based RIC regimen.from January 2008 to December 2017, were reviewed retrospectively. HSCT outcomes including engraftment, survival, and GVHD were analyzed. Results Nine patients were received HSCT using Bu/Flu based RIC regimen. Three patients received HSCT after diagnosis of familial HLH and the other 6 received after reactivation. All 3 patients with familial HLH had UNC13D mutations. Median 8.35 × 106 /kg (range, 2.84-10.05 × 106) CD34 positive cells were infused. All patients achieved WBC and PLT engraftment at median 11 days (range, 10-21) and 19 days (range, 13-32) from HSCT with full donor chimerism which sustained until last visit. Cyclosporine and mycophenolate mofetil were applied as GVHD prophylaxis except one patient who received HSCT from syngeneic sibling. Three patients (33%) experienced acute graft-versus-host disease (GVHD) of grade 2 which was well controlled after conventional steroid treatment. Two patients (22%) underwent chronic GVHD, and one of them died. One patient (11%) had reactivation 4 months after HSCT from syngeneic sibling donor, and died. The 5-year overall survival was 78%. Two patients died; one died of disease and the other died of treatment related mortality (TRM). No TRM other than chronic GVHD was existed. Conclusion Our experience suggests that Bu/Flu based RIC regimen can be effective option for pediatric patients with HLH who need HSCT showing durable chimerism and long-term survival with decreased toxicity.

Results: According to the World Health Organization (WHO) classifications for PTCL, 11 patients had PTCL, not otherwise specified (PTCL-NOS), 6 patients had extranodal natural killer/T-cell lymphoma, nasal type (ENKL), and 1 patient had subcutaneous panniculitis-like T-cell lymphoma. Patients were treated with various chemotherapeutic regimens. Of these 18 patients, 5 (27.7%) relapsed and 7 (38.9%) died from disease progression. Two relapsed patients received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). The 5-year event-free and overall survival rates were 43.2% and 66.7% in all cases, 45.5% and 54.5% in PTCL-NOS, and, 25.0% and 83.3% in ENKL, respectively.

Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of the 65 patients died: three of TRM and 12 of disease-related mortality. The 5-year OS and EFS were 78.0% and 72.0%, respectively, and the 5-year cumulative relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not influenced by cytogenetic group (intermediated vs. poor), donor type (related vs. unrelated), transplant type (myeloablative vs. reduced-intensity conditioning), or number of pretransplant chemotherapy cycles (≤3 vs. >3 cycles). The low TRM rate and encouraging outcomes suggest that HSCT may be a feasible treatment for pediatric patients with AML without favorable cytogenetics.

BACKGROUND The immune thrombocytopenia (ITP) criteria were newly standardized by the International Working Group. Thus, we analyzed the natural course of childhood chronic ITP to predict the prognosis based on the revised criteria. METHODS The medical records of children with chronic ITP from May 2000 to February 2013 in our institute were reviewed. RESULTS Forty-seven children with chronic ITP who were not undergoing corticosteroid therapy were included. Their initial platelet count was 23±25×10(9)/L, and age at diagnosis was 6.3±4.1 years. The follow-up period was 5.4±3.7 years. Among them, 44.7% (21/47) showed spontaneous remission and maintained a platelet count ≥100×10(9)/L. And 66.0% (31/47) maintained a platelet count ≥50×10(9)/L until the last follow-up date. The time periods required for the platelet count to be maintained ≥50×10(9)/L and ≥100 ×10(9)/L were 3.1±2.7 and 3.6±2.7 years. Age at diagnosis in the ≥50×10(9)/L group (5.7±4.4 years) was significantly lower than the age at diagnosis in the

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P

Introduction Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of Langerhans cells. The reported incidence of LCH ranges from 0.5-5.4 cases per million persons per year, according to the prospective registry-based reports. However, due to the rarity of the disease and the limitation of prospective registries, the comprehensive understanding of nation-wide epidemiology has been limited. This study aimed to analyze the incidence by age and diagnostic patterns of LCH using the population-wide healthcare database in Korea. M ethods The claims data of the Health Insurance Review and Assessment (HIRA) contain information of 46 million patients per year, which accounts for about 95% of the total population of South Korea. The data include information regarding diagnoses, hospitalization, and prescription drugs. Since 2005, the "National cancer registration and reimbursement program" has been implemented, which reimburse for 90% of the medical expenses of patients with malignant diseases, including LCH. Therefore, all the patients with LCH have been registered in the database after a definite diagnosis. From the HIRA open data source, we extracted a claim data of patients corresponding to diagnosis codes of C95.0 (Multifocal and multisystemic -disseminated LCH), C96.5 (Multifocal and unisystemic LCH), or C96.6 (Unifocal LCH) during the period of 2010-2017. Data for 2010-2011 was used as a reference for overlapping patients, and the actual analysis was conducted with data from 2012 to 2017. Results During the period, a total of 59,929 insurance statements were issued, and 53,446 statements with only one identical diagnostic code and confirmative workups were selected for final analysis. The total incidence cases during the period of 2012 to 2017 were 899 cases, and the average number of the annual incidence was 150 cases. The incidence was 3.0 cases per million persons per year. There was a male predominance with a male-to-female ratio of 1.63:1 (558 cases:341 cases) in a whole cohort. For the detailed diagnosis codes, C96.6 was the most frequent as 93.4%, followed by C96.0 as 4.9%, and C96.5 as 1.7%. The average age at diagnosis was 26.6 years (range, 0.2~87 years) in all incidence cases, and 26.6 years for C96.0 group, 29.5 years for C96.5 group, and 25.9 years for C96.6 group, respectively. When patients were grouped by age at diagnosis, the age group of 0-4 years showed the highest annual incidence of 17.9 cases per million, followed by the group of 5-9 years as 8.9 cases per million, and the age group over 70 years showed the lowest annual incidence of 1.1 cases per million (Figure 1). There were no seasonal trends in the diagnosis of LCH. At diagnosis, 21.6% of patients were diagnosed at the department of neurosurgery, 21.5% at pediatrics, 19.3% at internal medicine, and 16.8% at orthopedic surgery. For examinations conducted at the time of diagnosis, simple radiography was conducted in 84.9% of patients, computed tomography in 32%, magnetic resonance imaging in 39.6%, bone scan in 47.1%, and bone marrow examination in 22.9% of patients. For treatment, most of the patients (93.7%) received at least one modality of treatments after diagnosis; 42.7% of patients underwent surgery only, 30.4% received topical steroids only, 12.6% underwent surgery followed by chemotherapy, and 10.5% received chemotherapy. For chemotherapy, vinblastine was the most frequently prescribed drug as used in 82.9% of patients who received chemotherapy, followed by methotrexate in 39.4%, and mercaptopurine in 38.9%. Conclusions This study was the first big data analysis regarding LCH in Korea, and the annual incidence of LCH was 3.0 cases per million persons per year. The incidence was highest at 0-4 years of age, and the incidence was significantly decreased with age. We plan to conduct further research on the treatment and outcomes of Korean LCH patients in conjunction with the data of ongoing prospective registry. Figure 1. The annual incidence of Langerhans Cell Histiocytosis by age at diagnosis Figure 1 Disclosures No relevant conflicts of interest to declare.

Brentuximab vedotin (BV) is a monoclonal antibody-drug conjugate that targets CD30, and has been reported to be effective for relapsed/refractory anaplastic large cell lymphoma. We here report a patient who experienced multiple relapses after conventional chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). He achieved a complete metabolic response with BV and proceeded to undergo haploidentical HSCT. After HSCT, he received three doses of BV to prevent an early relapse, and remains in remission 16 months post-transplantation. Our case suggests the potential use of BV both as a bridging therapy to allogeneic HSCT and as a maintenance therapy post-transplantation.

Spinal involvement of Langerhans cell histiocytosis (LCH) affects morbidity, but outcomes are not well understood. We analyzed long-term outcomes following uniform treatment at a single institution. Clinical characteristics and outcomes of spinal LCH patients were retrospectively analyzed. Height ratios were calculated using the anterior height of the involved vertebral body on magnetic resonance imaging (MRI) and the expected normal vertebral height. Twenty-two (22.4%) of 98 patients diagnosed with LCH had spinal involvement. The median age at diagnosis was 4.1 (range 0.6–12.3) years. Thirty-one spinal lesions were identified in 22 patients; the thoracic spine (n = 17) was most commonly affected. Eight lesions with minimal collapse, which appeared normal on plain radiography, were detected with MRI. All patients received vinblastine-based chemotherapy. Fourteen (70%) of 20 evaluable vertebral body collapses, including eight severe lesions, showed improvement in vertebral body height at a median follow-up of 6.0 (range 2.8–12.0) years. All traceable patients were alive without disease. Long-term follow-up of vertebral body collapse revealed vertebral height improvement in approximately 70% of spinal LCH patients, even in severe cases. MRI at diagnosis detected spinal lesions earlier with higher sensitivity than plain radiography.

This study investigated the effect of a zinc-deficient diet on the hearing in CBA mice and aimed to verify whether this hearing change is reversible by supplementation of zinc afterwards. We assessed hearing through an auditory brainstem response (ABR) with tone burst stimulation in 4, 8, 16, and 32 kHz and distortion product otoacoustic emissions in 5.6, 8, 11.3, and 16 kHz every week. The ABR threshold started to increase after 4 weeks on a zinc-deficient diet. The difference in the threshold between control and zinc-deficient animals became greater over time and plateaued at about 6 weeks. The ABR threshold differences between control and zinc-deficient mice were greater at higher frequencies. Four weeks of normal diet, following 8 weeks of a zinc-deficient diet, restored the ABR threshold to normal at all measured frequencies. Zinc-deficient mice did not show any distortion product otoacoustic emission threshold change at all frequencies. This finding suggests that a zinc-deficient diet increased the ABR threshold in CBA mice and a zinc-adequate diet restored the ABR threshold to normal.

Background Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. Methods Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. Results Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). Conclusion CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.

Brentuximab vedotin (BV) is a monoclonal antibody-drug conjugate that targets CD30, and has been reported to be effective for relapsed/refractory anaplastic large cell lymphoma. We here report a patient who experienced multiple relapses after conventional chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). He achieved a complete metabolic response with BV and proceeded to undergo haploidentical HSCT. After HSCT, he received three doses of BV to prevent an early relapse, and remains in remission 16 months post-transplantation. Our case suggests the potential use of BV both as a bridging therapy to allogeneic HSCT and as a maintenance therapy post-transplantation.

Background and purpose: One of the key obstacles to successful haploidenitcal hematopoietic cell transplantation (HHCT) is a development of fatal GVHD. Although much progress in immunosuppressant (IS) has effectively prevented the development of acute GVHD, they have many serious toxicity and drug interactions requiring serial monitoring of drug levels. Recent advances in ex vivo depletion technique enabled to effectively reduce T cells or their subset, αβ+ T cells, leading to residual αβ+ T cells in grafts well below 5×104/kg of recipient weight. We eliminated post-transplant pharmacologic GVHD prophylaxis along with targeting αβ+ T cell dose ≤ 5×104/kg since November 2015. In this study, we compared early post-transplant outcomes between with (IS+) or without (IS-) post-transplant immunosuppressants after ex vivo αβ+ T cell-depleted HHCT. Methods: Between May 2012 and July 2016, 69 pediatric patients received HHCT using TCRαβ-depleted grafts from haploidentical family donors at Asan Medical Center Children's Hospital. Fifty patients received tacrolimus and mycophenolate mofetil to prevent acute GVHD, while 19 did not receive any immunosuppressant after transplant. All donors received G-CSF for 4 consecutive days and peripheral blood stem cells were collected on days -1 and 0. The αβ+ T cells were depleted by negative selection using the CliniMACS® system (Miltenyi-BioTec, Bergisch-Gladbach, Germany) according to manufacturer's instruction. In the earlier trial of IS+, the final doses of αβ+ T cells were adjusted to 1-5×105 cells/kg by add-back from the raw bag. Since November 2015, the cell dose was targeted at ≤ 5×104 αβ+T cells/kg with no post-transplant immunosuppressants (IS-). Results: The median infused CD34+ cells, αβ+ T cells, γδ+ T cells and CD3-CD56+ NK cells per kg of recipient weight were 8.9×106, 33.8×104, 20.0×106, 45.9×106 in IS+ group and 6.1×106, 4.6×104, 17.5×106, 24.6×106 in IS- group, respectively. All 69 patients achieved neutrophil engraftment at a median of 10 days (range, 9-17). Three patients out of 50 in IS+ group experience graft rejection (GR), while no GR occurred in IS- group. The cumulative incidences of acute GVHD grade II-IV were similar (31% vs 33%). Severe acute GVHD ≥ grade III developed in 7 in IS+ group, while none in IS- group developed ≥ grade III. As of July 2016, the median follow-ups were 24 months (range 9.5-50.8) for IS+ group and 5 months (0.5-9.1) for IS- group. Two out of 50 patients in IS+ group died of TRM leading to 2.2% at 6 months and 4.9% at 1 year after HHCT, while no patients in IS- group died of TRM during the follow-up period. The mean time from transplant to discharge were longer in IS+ group compared to IS- group (32 days versus 21 days, P=0.049). While the mean time of hospital stay within 100 days post-HHCT for patients who survived more than 100 days was not different between two groups (47 days versus 34 days, P>0.05). Conclusions: The major findings of our study were less severe acute GVHD and shorter hospital stay from HHCT to discharge in IS- group, even with less T cell dose, compared to IS+ group. Therefore, this HHCT using ex vivo αβ-depleted graft containing αβ+ T cells ≤ 5×104/kg is an effective treatment strategy to prevent acute GVHD without post-transplant IS. In addition, the early clinical outcomes were comparable between with and without post-transplant IS. Disclosures No relevant conflicts of interest to declare.

Background: Recent advances in haploidentical hematopoietic cell transplantation (HHCT) enabled this transplant using haploidentical family donor to be a viable option for pediatric patients lacking matched related or unrelated donor. In our center, HHCT using ex vivo T cell-depleted (TCD) grafts after reduced-intensity conditioning (RIC) was conducted since 2008. The safety and efficacy of this transplantation modality for pediatric with acute leukemia were investigated. Methods: Thirty-one pediatric patients with acute leukemia received ex vivo T cell-depleted HHCT at Asan Medical Center Children's Hospital between July 2008 and June 2016. Four patients received CD3-depleted grafts and 27 received TCRαβ-depleted stem cells. Among 31 patients, 9 had ALL (3 CR1, 6 CR2-3), 22 had AML (18 CR1-3, 4 NR). Seven patients had relapsed after previous allogeneic HCT. All 31 patients underwent a uniform RIC regimen consisting of low-dose total body irradiation (LD-TBI; 600 cGy), fludarabine (FLU; 180 mg/m2), cyclophosphamide (CY; 100 mg/kg), and rabbit anti-thymocyte globulin (r-ATG; 3 mg/kg). Results: The median age at HHCT was 14 years (range, 1-19). All 31 patients achieved sustained neutrophil engraftment at a median of 10 days (range, 9-17) post-transplant. The cumulative incidence of acute GVHD grade II-III and III were 30% and 21%, respectively. None developed grade IV. Two of 26 evaluable patients developed extensive chronic GVHD. As of July 2016, 18 of the 31 patients survive free of disease with a median follow-up of 26 months (range, 2-98 months). Ten patients have died. Causes of death were relapse (n=9) and disseminated tuberculosis (n=1). Only one patient died of non-relapse cause, leading to TRM of 5.3% at 1 year. EFS and OS at 2 years for all patients were 51% and 60%, respectively. Sixteen patients with AML who received a first HHCT in any CR showed a favorable outcome (EFS of 85%), whereas, 6 patients with ALL who received a first HHCT in CR showed a poor EFS of 28%. In addition, all patients (6 with AML and 3 with ALL) who received a subsequent HCT in CR or were not in remission developed relapse. Conclusions: This study demonstrated that our ex vivo T cell-depleted HHCT using RIC is a feasible therapy with low TRM for pediatric patients with acute leukemia. The outcome of patients with AML who received their first transplant in CR was excellent in this treatment modality. However, the outcome of ALL was poor suggesting that more intensified conditioning regimen may be required for those diseases. Furthermore, an innovative treatment strategy is warranted to improve the outcome for patients with relapsed or refractory acute leukemia. Disclosures No relevant conflicts of interest to declare.

Introduction : Clinical aspects and risk factors of Cytomegalovirus (CMV) reactivation and diseases are an emerging interest in recent investigation fields of hematopoietic stem cell transplantation (HSCT). Several risk factors and clinical manifestations of CMV infection have been reported in numbers of previous reports. Monitoring of viral replication and timely given antiviral agents have resulted in a decreased incidence of CMV-related death recently. However, CMV in still a major cause of infectious complications after HSCT. Specially in haploidentical HSCT setting, clinical manifestations and associated risk factors have been rarely reported. This study is conducted to identify risk factors and clinical aspects of CMV reactivation and disease in pediatric haploidentical HSCT. Methods : We retrospectively reviewed the medical records of 92 pediatric patients who underwent haploidentical HSCT using ex vivo T cell-depleted grafts at Asan Medical Center between December, 2004 and June, 2016. After haploidentical HSCT, all recipients were monitored for CMV infection by CMV pp65 antigen and/or CMV-PCR. Both recipient and donor were screened for CMV serology before the HSCT. During the study period, methodologic changes in ex vivo T cell depletion and CMV prophylaxis policy have been modulated with the course of time. During the 1st study period (Group I, n=19), CD3+ T cell was depleted without CMV prophylaxis while ganciclovir for CMV prophylaxis was given with CD3+ T cell depletion during the 2nd period (Group II, n=16). The T cells expressing alpha-beta T cell receptor (TCRαβ) was depleted during the 3rd period (Group III, n=57) with ganciclovir prophylaxis. Results : Of the 92 patients, 49 (53.3%) developed CMV reactivation after haploidentical HSCT. CMV reactivation significantly reduced in group II and III compared to group I (84±8.4% vs 46±5.9%; p Conclusions : Our study demonstrated that ganciclovir prophylaxis has effectively reduced the occurrence of CMV reactivation in ex vivo T cell depleted haploidentical HSCT. In addition, close monitoring of CMV pp65 antigen and timely preemptive management is important to prevent CMV related death. Disclosures No relevant conflicts of interest to declare.

Background: Hematopoietic stem cell transplantation (HSCT) remains the preferred frontline curative modality for patients with aplastic anemia in the presence of a matched familial donor (MFD). In the absence of MFD, the general consensus is frontline immunosuppressive therapy followed by HSCT from a matched unrelated donor (MUD) in case of failure or relapse, and recently haploidentical family donor (HFD) is emerging as an alternative donor in aplastic anemia. We evaluated the outcome of HSCT in children and adolescents with acquired severe aplastic anemia (SAA), and compared outcomes of transplantation according to the donor types. Methods : We performed a retrospectively analysis of 61 patients with acquired SAA at a single center between July 1998 and May 2016. Conditioning regimen was a reduced-intensity combination of fludarabine, cyclophosphamide, and rabbit anti-thymocyte globulin in most cases, and low dose total body irradiation was added for haploidentical hematopoietic stem cell transplantation (HHCT). Grafts for HHCT were manipulated by ex vivo T-cell depletion. Results: Of the 61 patients reviewed, total 66 HSCTs were done. The median age at HSCT was 12.5 years (range, 0.7-21.7 years). By donor types, 15 patients received grafts from MFD, 20 from MUD, and 26 from HFD. Grafts for HHCTs were CD3-depleted in 12 patients, CD3/CD19-depleted in 4, and ¥á¥â+ T-cell depleted in 10 patients. Among 61 patients, 59 patients achieved neutrophil engraftment at a median of 11 days (range, 9-18 days). The medians of neutrophil engraftment were 10 days in HFD recipients, 13 days in MFD and 12 days in MUD HSCTs, respectively, and HHCT group had significantly faster neutrophil engraftment than others (Figure 1). There were 9 patients who experienced graft failure (GF) among 61 patients. Of the 35 patients with matched donors, 1 patient failed to achieve primary engraftment, and 3 experienced graft rejection after engraftment. Of the 26 HFD recipients included, neutrophil engraftment was achieved in 25 patients, except 1 patient. Additional 4 HHCT recipients experienced graft rejection within 1 month post-HHCT. Five (1 MUD, 4 HFD) out of 9 patients who experienced GF received a second HSCT and achieved sustained engraftment, another 1 patient was alive without transfusion or further treatment, and the other 3 patients died after GF. A total of 18 patients developed grade II-IV acute GvHD (13 with grade II and 5 with grade III); 9 had received MUD transplant, 7 HFD, and 2 MFD. Seven patients developed chronic GvHD; 4 patients were MUD recipients, and 3 HFD. The cumulative incidence (CI) of grade II-III acute GvHD was 34% (MUD : 45%, HFD : 33.3%, MFD : 16.7%), and 1-year CI of chronic GvHD was 14.4%. There was no statistically significant difference in GvHD occurrence according to the donor types. As for survival results, total four patients died; one HFD recipient died of CMV pneumonia on day +157 of HHCT, and other 3 patients (1 MFD, 1 MUD, 1 HFD) died after GF. Two out of these 3 patients received a second HSCT; one MUD recipient died of acute respiratory distress syndrome and acute renal failure, and another HFD recipient died of pure red cell aplasia. The other MFD recipient died of poor graft function after GF. The overall transplant-related mortality was 7.6%. At a median follow up 45.7 months (range, 1.5-195.2 months), the estimated 5-year overall survival (OS) was 92.7% in 61 patients. There was no statistical difference in OS among HSCTs from three different donor types (MFD : 92.9% vs MUD : 94.4% vs HFD : 91.3% at 5 years, respectively, p value = 0.915) (Figure 2). Conclusions: Our study demonstrated that survival outcomes of HHCT were comparable to HSCT from matched familial or matched unrelated donors in pediatric patients with acquired SAA. HHCT was associated with rapid neutrophil recovery, and tolerable treatment related toxicities in SAA patients. These data suggest that hematopoietic stem cell transplantation from haploidentical family donors is a reasonable therapeutic option for children and adolescents with acquired SAA. Disclosures No relevant conflicts of interest to declare.

Hypothesis Cigarette smoking may potentiate noise-induced hearing loss. Background Many epidemiological studies have shown that cigarette smoking is a major risk factor for noise-induced hearing loss. Methods BALB/c mice were exposed to passive smoking for 2 h/d for 2 weeks before exposure to 110-dB sound pressure level white noise for 3 hours once. Hearing was assessed via the auditory brainstem response with tone-burst stimulation and distortion product otoacoustic emissions before and at 1, 3, 5, 7, 14, 21, and 28 days after noise exposure. Oxidative stress and hypoxia were assessed by immunostaining with 8-oxoG and hypoxia-inducible factor 1α, respectively. Results Control mice unexposed to both smoking and noise and mice exposed to smoking only showed no shift in hearing threshold. In contrast, mice exposed to noise only or smoking plus noise showed abrupt increases in hearing threshold. In mice exposed to noise only, hearing threshold returned to prenoise levels after 2 weeks. However, in mice exposed to smoking plus noise, the loss of hearing was significantly higher, and hearing threshold did not return to the pre-exposure levels until 4 weeks later. Positive staining with 8-oxoG and hypoxia-inducible factor 1α were observed in the inner ear of the smoking-only and smoking-plus-noise group similar to noise-only mice, whereas no positive staining was observed in control group. Conclusion These results indicate that cigarette smoking may potentiate the harmful effects of noise on hearing and disturb the recovery mechanism in the cochlea.

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is the preferred curative therapy for children with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We evaluated the treatment outcomes of children with Ph+ ALL who underwent allogeneic HSCT. Methods Fifteen children diagnosed with Ph+ ALL in Asan Medical Center Children's Hospital between 1998 and 2012 were retrospectively analyzed. Results Of 521 children diagnosed with ALL during the study period, 15 had a Philadelphia chromosome. Among these 15 patients, 13 attained complete remission (CR) following induction chemotherapy, and two died of intracerebral hemorrhage during leukapheresis and induction chemotherapy, respectively. Of the 13 patients who attained CR, 12 received allogeneic HSCT, mainly from unrelated donors. Of the 12 patients who received HSCT, one died of a transplant-related cause, one died of relapse after HSCT, and 10 remain in continuous CR. Of the 10 patients who remained in CR longer than six months after HSCT, seven received post-HSCT imatinib. For all 15 patients, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 60.0%, 48.6%, and 38.8%, respectively, with a median follow-up of 70 months. For the HSCT group, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 80.2%, 72.9%, and 29.3%, respectively, with a median follow-up of 100 months. Conclusion Allogeneic HSCT cures a significant proportion of Ph+ ALL patients. Because the use of imatinib appears to be a promising approach, strategies that include tyrosine kinase inhibitors before and after HSCT require further evaluation.

Currently, haploidentical hematopoietic cell transplantation (HHCT) is considered an established option for patients who have diseases curable with HCT but who lack a suitable donor. We compared the early post-transplant outcomes of the two transplant groups using different in vitro depletion method. Between July 2008 and June 2014, 49 pediatric patients underwent in vitro T cell-depleted HHCT. Of 49 patients, 28 received CD3-depleted stem cells (CD3-HHCT) and 21 received TCRαβ-depleted grafts (TCRαβ-HHCT). Among 28 patients of CD3-HHCT, nine had hematologic malignancy [HM, one with ALL in non-CR, six with AML (3 CR1, 2 CR2, 1 non-CR), and two with MDS-RCMD], 18 had non-malignant disease (one with Fanconi anemia, 16 with acquired SAA, and one with CDA), and one had refractory neuroblastoma. Among 21 patients of TCRαβ-HHCT, 16 had HM [five with ALL (2 CR1, 2 CR2, 1 CR3), five with AML (2 CR1, 2 CR2, 1 non-CR), one with mixed lineage leukemia in non-CR, one with MDS-RCC, two with JMML, and two with NHL (1 CR2, 1 CR3)], two had SAA, and three had solid tumors [two with RMS (1 CR2, 1 refractory), and one with Ewing sarcoma in CR3]. Of 28 patients who received CD3-HHCT, two patients failed to achieve primary engraftment, and five patients experienced graft rejection (GR) within 28 days post-transplant. No patients of TCRαβ-HHCT experienced graft failure (GF). Early GF (primary GF and GR) was more common in CD3-HHCT compared to TCRαβ-HHCT (P=0.011). The cumulative incidence of acute GVHD ≥ grade II was comparable between two groups (33.3% for CD3-HHCT and 27.0% for TCRαβ-HHCT). Extensive chronic GVHD occurred in three patients from CD3-HHCT and one from TCRαβ-HHCT. T and T4 cell counts at 2 months post-transplant were higher in TCRαβ-HHCT than that of CD3-HHCT (P=0.007 for T and P=0.074 for T4). In CD3-HHCT, four patients died of non-relapse causes (two of CMV disease, one of encephalopathy, and one of autoimmune hemolytic anemia) and one died of leukemia. In contrast, five patients from TCRαβ-HHCT died of disease but, none died of non-relapse cause. Of 20 patients (18 from CD3-HHCT and two from TCRαβ-HHCT) with non-malignant disease, only one patient of CD3-HHCT died of TRM. As for 29 patients (10 from CD3-HHCT and 19 from TCRαβ-HHCT) with malignant disease, the EFS at 1 year for CD3-HHCT and TCRαβ-HHCT were 60.0% and 56.6%, respectively (P>0.05). In this study, TCRαβ-depleted HHCT showed a better early post-transplant outcome in terms of engraftment, immune recovery, and NRM, compared to CD3-HHCT. However, further study is warranted to evaluate the efficacy of TCRαβ-HHCT in preventing relapse in advanced malignancy. Disclosures No relevant conflicts of interest to declare.

Background: Hematopoietic Stem Cell Transplantation (HSCT) from a matched sibling donor (MSD) is the treatment of choice for pediatric patients with severe aplastic anemia (SAA). On the other hand, HSCT from alternative donor (AD-HSCT) is indicated as salvage therapy for patients who failed immunosuppressive therapy (IST) without MSD. However, the outcomes of alternative donor HSCT have been improved with recent advances in HSCT techniques. Therefore the indication of alternative donor HSCT in SAA needs to be reevaluated. Methods: We retrospectively reviewed the medical records of 45 pediatric patients with SAA who received HSCT at Asan Medical Center Children’s Hospital from February 2001 to January 2014. To analyze the efficacy of HSCT from alternative donors, we compared overall survival, incidence of acute and chronic GVHD, incidence of graft failure (GF), and incidence of post HSCT infections including CMV reactivation, PTLD, bacteria and fungi according to the type of donors. Results: Of the 45 patients, 32 were male and 13 were female. Median age at diagnosis was 8.0 years (range, 0.2-17.0). Median age at HSCT was 12.9 years (range, 0.7-21.7). Median CD34+ cell dose was 7.64 X 106 /kg (range, 2-33.8). Ten patients received HSCT from MSD (MSD-HSCT), 15 patients from URD (URD-HSCT) and 20 patients from haploidentical family donor (HFD-HSCT). Twenty-six patients (55.3%) had received IST prior to HSCT. Of 45 patients, eight patients experienced GF (one from MSD, one from URD, and six from HFD). Cumulative incidence (CI) of GF was higher in HFD-HSCT compared to the other type of HSCT (30% vs 8%, P=0.049). Among the 8 patients, 6 patients achieved engraftment after additional HSCT, one died of infection after GF and the remaining one patient was waiting for the second HSCT. The CIs of acute GVHD were 20% for MSD-HSCT, 60% for URD-HSCT and 40% for HFD-HSCT, respectively (P>0.05). The CIs of chronic GVHD were 10% for MSD-HSCT, 46% for URD-HSCT and 16% for HFD-HSCT, respectively (P>0.05). Twenty-two patients developed CMV reactivation, 7 had PTLD and 13 had bacterial infection after HSCT. CI of CMV reactivation was higher in AD-HSCT than that of in MSD (63% vs 0%, P=0.002). Three patients (one with MSD-HSCT, one with URD-HSCT and one with HFD-HSCT) died at 81 days, 405 days, and 456 days after transplantation. Of the three patients, one died of acute GVHD, one died of autoimmune hemolytic anemia and the remaining one died of infection after GF. At a median follow-up of 40.8 months (range, 6.5-162.8), 3 year-OS of all 45 patients was 92.9% (100% for MSD-HSCT, 92.3% URD-HSCT and 89.4% for HFD-HSCT, P>0.05). All survived 42 patients were transfusion-independent. Conclusions: In our study, we suggest that early alternative HSCT including HFD-HSCT could be beneficial to the children with SAA who do not have MSD. However, a larger multicenter study is needed to verify our results. Disclosures No relevant conflicts of interest to declare.

Background Anaplastic large cell lymphoma (ALCL) is uncommon in children, accounting for approximately 15% of all cases of childhood non-Hodgkin lymphoma. Despite many studies attempting new treatment strategies, treatment outcomes have not significantly improved, and the optimal treatment for pediatric ALCL has not been established. Methods The records of newly diagnosed ALCL patients at our institute between July 1998 and April 2013 were reviewed. We evaluated the general characteristics of the patients, chemotherapy regimens, overall survival (OS) rates, and event-free survival (EFS) rates. Results Twenty-eight ALCL patients were eligible. The median age at diagnosis was 10.8 years. Lymph node involvement was the most common presentation (79%). CCG-5941, a multi-agent T-cell lineage chemotherapy, was the predominant treatment regimen (57%). The five-year OS and EFS rates were 88% and 69%, respectively. Stage, the presence of B symptoms, lung involvement, and bone marrow involvement were significant prognostic factors for EFS (P=0.02, 0.01, 0.01, and 0.02, respectively). Eight patients relapsed, and three died during the study period. Four of the eight patients who relapsed were treated with high-dose chemotherapy and autologous stem cell transplantation (HDCT-ASCT). Two of the four who had undergone HDCT-ASCT developed secondary relapses and were subsequently treated with allogeneic SCT or brentuximab. Conclusion We found that treatment outcomes with multi-agent chemotherapy in children with ALCL were similar to those of previous reports, and that relapsed patients could be salvaged with HDCT-ASCT or allogeneic SCT. A prospective, larger cohort study is warranted to define the optimal treatment for pediatric ALCL.

Background Continuous infusion of factor VIII (FVIII) is a more cost-effective method for treating hemophilia A than intermittent bolus injection. However, there is currently no specific data in Korea about the progress of in vitro FVIII coagulant activity (FVIII:C) after reconstitution from its lyophilized form. Methods Three commercial FVIII concentrate products (two recombinant FVIII and one plasma-derived) were used. In vitro FVIII:C was measured at 0, 2, 4, 6, and 8 hours following reconstitution in both the indoor light-exposed and light-shielded groups. Results For the three drugs, in vitro FVIII:C decreased over the 8 hours following reconstitution (P

Background and Objectives: The aim of this study was to investigate the relationship between inhalation anesthetics and hearing in mice. Materials and Methods: As inhalation anesthetics, isoflurane was used. Auditory brainstem response and distortion product otoacoustic emission were used as measurement of hearing. Mice were divided into 2 groups. 'Isoflurane group' consisted of mice that were anesthetized with an inspired concentration of 2.0 vol% isoflurane with 2 L/min of oxygen (n=10). 'Control group' consisted of mice that were anesthetized with ketamine and xylazine (n=10). Results: Auditory brainstem response thresholds in mice anes- thetized with ketamine and xylazine was not different from those in mice anesthetized with iso- flurane. Threshold of DPOAE was higher in mice with isolurane than with ketamine and xyla - zine. Changes of efferent control may be induced by isoflurane and consequently change the threshold of DPOAE in mice. Conclusions: These results infer that, there was a change of cen- tral nervous system induced by inhalation anesthetics, this change also can be applied to the strategies for prevention of hearing loss. Korean J Audiol 2012;16:14-17

Purpose: This study evaluated the efficiency and safety of the Foley catheter for esophageal removal of coins in children, compared to standard endoscopic extraction with respect to success rate, sedation, promptness and cost. Methods: Twenty four children with coin lodgement in esophagus were managed with either a Foley catheter (n=14) or endoscopic extraction (n=10) from January 2007 through August 2010 at Kyungpook National University Hospital. A retrospective review of medical records and radiological findings was performed. Results: Of the 14 patients who underwent Foley catheter extraction, successful and complication-free removal was achieved in 10 cases (71.4%). Of the 10 patients who underwent endoscopic extraction, all cases were successful (p=0.114). Sedation rate in the Foley catheter and endoscopic extraction group was 6/14 and 10/10 (p=0.006). The average wait time before the procedure and average hospital charge (US$) were 2.0±1.1 hours and 18.1±13.7 hours, and $113 and $428 for Foley catheter extraction and endoscopic extraction, respectively. Conclusion: Foley catheter extraction may be tried for the removal of esophageal coins in uncomplicated children. The technique is effective, safe, inexpensive and free of general anesthesia. (Korean J Pediatr Gastroenterol Nutr 2011; 14: 251∼257)