Ki Woong Sung

Mesenchymal stem cells feeder layer from human umbilical cord blood for ex vivo expanded growth and proliferation of hematopoietic progenitor cells.

Ex vivo expansion of hematopoietic stem cells was suggested as the best way of overcoming problems caused by limited hematopoietic cell number for cord blood transplantation. In this study, we quantified and characterized an ex vivo expansion capacity of umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) as a cell feeder layer for support of UCB-derived committed hematopoietic progenitor cells (HPCs) in the absence or presence of recombinant cytokines. The UCB-derived MSCs used in the study differentiated into osteoblast, chondrocytes, and adipocytes under proper conditions. Frequencies in colony forming unit-granulocyte, macrophage, colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte, burst forming unit-erythrocyte, and colony forming unit-erythrocyte increased to 3.46-, 9.85-, 3.64-, and 2.03-folds, respectively, only in culture supplemented by UCB-derived MSCs as a cell feeder layer without recombinant cytokines (culture condition C). Identified expansion kinetics in all kinds of committed HPCs showed plateaus at 7 culture days, suggesting some consumable components were required for the expansion. Physiological importance and different roles for different committed HPCs of UCB-derived MSCs as a cell feeder layer were revealed by a distinguished expansion capacity for colony forming unit-megakaryocyte. The preferred maintenance of CD33−CD34+ in culture condition C was also identified. The presence of cobblestone-like areas as hematopoietic microenvironment and various cell feeder layer-originated hematopoietic cytokines including interleukin-1β and granulocyte, macrophage-colony stimulating factor were suggested as underlying mechanisms for the identified expansion capacity. The present numeric and biological information about intrinsic expansion capacity for UCB-derived committed HPCs will increase further biological and clinical applications of UCB-derived MSCs.

Stem and progenitor cells in human umbilical cord blood

Both stem cells and progenitor cells are present in umbilical cord blood (UCB) at a high frequency, making these cells a major target population for experimental and clinical studies. As the use of autologous or allogeneic hematopoietic stem cell transplantation in the treatment of various diseases has grown rapidly in recent years, the concept of UCB banking for future use has drawn increasing interest. Stem and progenitor cells derived from UCB offer multiple advantages over adult stem cells, such as their immaturity (which may play a significant role in reducing rejection after transplantation into a mismatched host) and ability to produce large quantities of homogeneous tissue or cells. These cells can also differentiate across tissue lineage boundaries into neural, cardiac, epithelial, hepatic, and dermal tissues. Human UCB provides an alternative cell source that is ethically acceptable and widely supported by the public. This paper summarizes the characteristics of human UCB-derived stem and progenitor cells and their potential therapeutic use for tissue and cell regeneration.

Loss of heterozygosity analysis of chromosome 17p13.1-13.3 and its correlation with clinical outcome in medulloblastomas.

Cytogenetic and molecular genetic studies have shown that deletions on the short arm of chromosome 17 distal to p53 locus are the most common genetic events in medulloblastoma. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1–13.3 by loss of heterozygosity (LOH) analysis to investigate the possible involvement of 17p13.1–13.3 in medulloblastoma development. We also performed survival analysis to determine whether LOH analysis of 17p13.1–13.3 can be used to predict prognosis in medulloblastoma.Loss of heterozygosity was analyzed by polymerase chain reaction on chromosome 17p13.1–13.3 using three microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1–13.2, and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted either from archival tissue or fresh frozen tissue specimens.Allelic deletions were detected in five of 17 informative cases (29%) on TP53, eight of 17 informative cases (47%) on D17S796, and four of 17 informative cases (24%) on D17S1574. Overall, nine of 17 cases (53%) showed LOH on chromosome 17p13.1–13.3. The 5-year progression free survival (PFS) and 5-year overall survival rates were identical (59%). The 5-year PFS for nine medulloblastoma patients with LOH on 17p13.1–13.3 was 56%, and the 5-year PFS for eight medulloblastoma patients without LOH on 17p13.1–13.3 was 63%. In our survival analysis, we did not find a significant association between survival and LOH on 17p13.1–13.3.Our results support the notion that deletions of chromosome 17p13.1–13.3 may be involved in the pathogenesis of medulloblastoma. From survival analysis, we conclude that LOH on chromosome 17p13.1–13.3 may not be a significant predictor of prognosis in medulloblastoma.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

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<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ⩽2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO+ patients and reduce reactivation in younger patients with MS involvement.

Atypical basal ganglia germinoma presenting as cerebral hemiatrophy: diagnosis and follow-up with 11C-methionine positron emission tomography

ObjectsSome basal ganglia germinomas are difficult to diagnose in early stage of disease due to vague initial presentation without discernable mass lesion on brain imaging. We performed this study to determine the usefulness of 11C-methionine positron emission tomography (MET PET) for the diagnosis and monitoring of disease activity.Materials and methodsMET PET was performed in three consecutive patients; they presented with cerebral hemiatrophy without definite mass lesions on brain image. The maximum standard tracer uptake values (max SUVs) were calculated and used for the quantitative evaluation of the abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy using MET PET/computed tomography. The max SUVs significantly decreased after treatment.ConclusionBasal ganglia germinoma should be considered in the differential diagnosis of patients with progressive hemiparesis and hemiatrophy on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can be valuable in evaluation of treatment effects and monitoring for tumor recurrence.

Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO).

Purpose Aplastic anemia (AA) is a rare hematologic disease characterized by pancytopenia and hypocellular marrow. The Korean Society of Pediatric Hematology Oncology investigated retrospectively the incidence, survival, and transfusion independency according to treatment strategies in AA. Methods All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data. Results The male and female ratio was 1.2, and the median age at diagnosis was 9.3 years. The annual incidence of Korean children with AA was 5.16 per million per year. Constitutional anemia was diagnosed in 44 children. In acquired AA, causes were identified in 39 children. Severe AA (SAA) at initial diagnosis was more common than nonsevere AA. The overall survival was 47.8% with supportive care, 68.1% with immunosuppressive therapy (IST), and 81.8% with hematopoietic stem cell transplantation. In IST, response rate was 65.7%, and relapse rate after response was 54.4% within a median of 23.0 months. The factors with overall survival were severity of disease in supportive care, severity and response in IST, donor type, graft failure, and posttransplant events in hematopoietic stem cell transplantation. Conclusions Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.

Incorporation of high-dose (131) I-metaiodobenzylguanidine treatment into killer immunoglobulin-like receptor/HLA-ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation.

We performed a pilot study (NCT 00793351) to evaluate the effectiveness and feasibility of a strategy incorporating high‐dose 131I‐metaiodobenzylguanidine (HD‐MIBG) treatment into killer immunoglobulin‐like receptor (KIR)/HLA‐ligand mismatched haploidentical stem cell transplantation (haplo‐SCT) in improving the survival of children with neuroblastoma who failed previous tandem autologous SCT.

Late‐onset noninfectious interstitial lung disease following autologous haematopoietic stem cell transplantation in paediatric patients

High‐dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT) is widely used in paediatric cancer patients, but few data about noninfectious interstitial lung disease (ILD) following this treatment are available. Therefore, we aimed to evaluate the incidence, clinical features and risk factors of noninfectious ILD after HDCT in paediatric patients.

ARID1B alterations identify aggressive tumors in neuroblastoma

Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

Erratum: Retrospective analysis of treatment outcome of pediatric ependymomas in Korea: Analysis of Korean multi-institutional data (Journal of Neuro-Oncology (2013) 113 (39-48) (DOI 10.1007/s11060-013-1087-5))

Primary intramedullary spinal cord tumors are a rare entity, comprising 4–10 %of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973–2008), and evaluates the impact of demographic and treatment factors on survival. Eighty nine adults were evaluated (mean age of 43 years); 49 % of patients had anaplastic astrocytoma and 51 % of patients had glioblastoma.88 % of patients had surgical intervention and 85 % of patients had radiotherapy. In univariate analysis, male gender (HR = 0.50, CI: 0.29–0.86, P = 0.01), surgical treatment (HR = 0.37, CI: 0.15–0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06–3.18, P = 0.03) were significant predictors of survival. Results remained significant or marginally significant after multivariate adjustment analyses. Adjuvant radiotherapy and age at diagnosis did not have a significant influence on survival. Future prospective studies from collaborative institutions combining richer detail in perioperative treatment, radiotherapy dosing, chemotherapy treatment, neurologic examinations, functional outcomes, and quality of life measures would contribute to more concrete, evidence-based treatment protocols for adult patients with primary malignant spinal cord astrocytomas.