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Abstract: Background: Epidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients (<19 years). Methods: In a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms. Results: A total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221 days (range, 7‐596 days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft‐vs‐host disease were associated with viremia (P = .028 and P = .006, respectively). Conclusions: Compared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea. [ABSTRACT FROM AUTHOR]

The article discusses the case of two Korean patients diagnosed with Upshaw-Schulman syndrome (USS), a form of congenital thrombotic thrombocytopenic purpura (TTP), caused by novel mutations in the ADAMTS13 gene. A 12-month-old girl received intravenous immunoglobulin, which increased her platelet counts, for idiopathic thrombocytopenic purpura (ITP). A 59-year-old was treated with plasma exchange and on routine follow-up under prophylactic infusion of fresh frozen plasma.

Background: In this study, we report the follow‐up results of reduced dose of craniospinal radiotherapy (CSRT) followed by tandem high‐dose chemotherapy (HDCT) in patients with high‐risk medulloblastoma (MB). Methods: Newly diagnosed high‐risk MB patients (metastatic disease, postoperative residual tumor >1.5 cm2, or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre‐RT chemotherapy, radiotherapy (RT) including reduced‐dose CSRT (23.4 or 30.6 Gy), four cycles of post‐RT chemotherapy, and tandem HDCT were administered. NanoString and DNA sequencing were performed using archival tissues. Results: In all, 40 patients were enrolled, and molecular subgrouping was possible in 21 patients (2 wingless, 3 sonic hedgehog, 8 Group 3, and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (5‐year cumulative incidence [CI] 10.4 ± 0.3%). However, six patients died from treatment‐related mortality (TRM) (four acute TRMs and two late TRMs) resulting in 18.5 ± 0.5% of 5‐year CI. Taken together, the 5‐year event‐free survival and overall survival were 71.1 ± 8.0% and 73.2 ± 7.9%, respectively. Late effects were evaluated in 25 patients and high‐tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common. Conclusions: The strategy using tandem HDCT following reduced‐dose CSRT showed promising results in terms of low relapse/progression rate; however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can benefit from HDCT will be needed in the future study. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to explore the roles of N‐myc and caspase‐8 in TRAIL‐resistant IMR‐32 cells which exhibit MYCN oncogene amplification and lack caspase‐8 expression. Materials and methods: We established N‐myc–downregulated IMR‐32 cells using shRNA lentiviral particles targeting N‐myc and examined the effect the N‐myc inhibition on TRAIL susceptibility in human neuroblastoma IMR‐32 cells expressing caspase‐8. Results: Cisplatin treatment in IMR‐32 cells increased the expression of death receptor 5 (DR5; TRAIL‐R2), but not other receptors, via downregulation of NF‐κB activity. However, the cisplatin‐mediated increase in DR5 failed to induce cell death following TRAIL treatment. Furthermore, interferon (IFN)‐γ pretreatment increased caspase‐8 expression in IMR‐32 cells, but cisplatin failed to trigger TRAIL cytotoxicity. We downregulated N‐myc expression in IMR‐32 cells using N‐myc–targeting shRNA. These cells showed decreased growth rate and Bcl‐2 expression accompanied by a mild collapse in the mitochondrial membrane potential as compared with those treated with scrambled shRNA. TRAIL treatment in N‐myc–negative cells expressing caspase‐8 following IFN‐γ treatment significantly triggered apoptotic cell death. Concurrent treatment with cisplatin enhanced TRAIL‐mediated cytotoxicity, which was abrogated by an additional pretreatment with DR5:Fc chimera protein. Conclusions: N‐myc and caspase‐8 expressions are involved in TRAIL susceptibility in IMR‐32 cells, and the combination of treatment with cisplatin and TRAIL may serve as a promising strategy for the development of therapeutics against neuroblastoma that is controlled by N‐myc and caspase‐8 expression. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas. [ABSTRACT FROM AUTHOR]

Abstract: A 17‐year‐old male with acute lymphoblastic leukemia developed severe hematuria and scrotal swelling after haploidentical hematopoietic cell transplantation (HCT). Urine culture was negative. BK virus and adenovirus were negative. However, Ureaplasma urealyticum was detected. He showed dramatic improvement after doxycycline treatment. This is the first report in the literature of hemorrhagic cystitis caused by U. urealyticum in a HCT recipient. In HCT recipients with hemorrhagic cystitis, U. urealyticum should be considered as a potential cause. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm−2. After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis ( HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. Methods The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011. Results In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system ( CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The 5-yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5-yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome. Conclusion Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein-Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments. [ABSTRACT FROM AUTHOR]

This study analyzes the data reported to the Korean Cord Blood Registry between 1994 and 2008, involving children and adolescents with non-malignant diseases. Sixty-five patients were evaluated in this study: SAA (n = 24), iBMFS, (n = 16), and primary immune deficiency/inherited metabolic disorder (n = 25). The CI of neutrophil recovery was 73.3% on day 42. By day 100, the CI of acute grade II-IV graft-versus-host disease was 32.3%. At a median follow-up of 71 months, five-yr OS was 50.7%. The survival rate (37.5%) and CI of neutrophil engraftment (37.5%) were lowest in patients with iBMFS. Deaths were mainly due to infection, pulmonary complications, and hemorrhage. In a multivariate analysis, the presence of >3.91 × 105/kg of infused CD34 + cells was the only factor consistently identified as significantly associated with neutrophil engraftment (p = 0.04) and OS (p = 0.03). UCBT using optimal cell doses appears to be a feasible therapy for non-malignant diseases in children and adolescents for whom there is no appropriate HLA-matched related donor. Strategies to reduce transplant-related toxicities would improve the outcomes of UCBT in non-malignant diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: In patients with high-risk neuroblastoma, the reduction in primary tumor volume was measured during the early phase of induction chemotherapy as an indicator of early tumor response, and the authors investigated whether the degree of tumor volume reduction could predict outcome in these patients. METHODS: Primary tumor volumes were measured both at diagnosis and at the first tumor response evaluation (after 2 or 3 cycles of induction chemotherapy) in 90 patients with high-risk neuroblastoma who had volumetrically evaluable computed tomography or magnetic resonance scans. If the tumor volume at the first response evaluation was >40% of the initial tumor volume, then the patient was categorized as a poor responder; otherwise, the patient was categorized as a good responder. Outcomes were compared according to the degree of tumor volume reduction at the first response evaluation. RESULTS: The tumor volume reduction was greater in patients who remained relapse free than in patients who had a relapsed tumor (median percentage tumor volume, 21% vs 41.5%; P = .037). The 5-year relapse-free survival rate was higher in the good responders than in the poor responders (83% [95% confidence interval, 72%-94%] vs 51% [95% confidence interval, 31%-71%]; P = .002). In a multivariate analysis of relapse-free survival, a poor early response was identified as an independent, unfavorable prognostic factor (hazard ratio, 4.24; 95% confidence interval, 1.59-11.29; P = .004). CONCLUSIONS: A greater reduction in tumor volume reduction the early phase of induction chemotherapy was associated with a better outcome in patients with high-risk neuroblastoma. Tailoring treatment intensity according to the early tumor response to induction chemotherapy may improve patient outcomes. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Respiratory viruses ( RVs) are a known cause of morbidity and mortality after hematopoietic stem cell transplantation ( HSCT). In this retrospective study, we focused on the first 28 d after transplantation in pediatric HSCT recipients and showed that a multiplex PCR assay significantly increased RV detection compared with a viral culture method. Among 176 pediatric HSCT recipients, 84 with respiratory symptoms within one yr after HSCT were tested by viral culture or multiplex PCR. Within 28 d after HSCT, nine patients were infected with RVs; the incidence of a first episode of RV infection within 28 d after HSCT was 5.1%. Eight patients recovered without complications. However, one patient died of adenovirus ( Ad V) pneumonia with pulmonary hemorrhage; the mortality rate of RV infection within 28 d after HSCT was 0.57%. In the nine patients with RV infection, five different types of RV were identified, either alone or with another RV. These were corona virus ( Co V), rhinovirus ( Rh V) and respiratory syncytial virus combined with Co V; Ad V combined with Rh V; and parainfluenza virus. Viral culture detected only one case of RV infection, while multiplex PCR detected eight, suggesting that screening of respiratory infections using multiplex PCR is better than the conventional culture method. [ABSTRACT FROM AUTHOR]

Lee SH, Paik KH, Sung KW, Son MH, Yoo KH, Koo HH, Kim JY, Cho EJ. Renal function after tandem high-dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. Pediatr Transplantation 2011: 15: 855-860. © 2011 John Wiley & Sons A/S. Abstract: Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high-risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of β- N-acetylglucosaminidase and β2-microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow-up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor. [ABSTRACT FROM AUTHOR]

The role of unrelated donor HSCT for children with de novo AML in CR1 is controversial. We performed this study to investigate the feasibility of unrelated donor HSCT who initially had intermediate‐ or high‐risk cytogenetics. We retrospectively reviewed medical records of patients with AML who received unrelated HSCT in CR1 at Samsung Medical Center between November 2001 and January 2012. Patients were allocated based on karyotype at diagnosis as follows: (a) low‐risk: inv(16), t(16;16), t(8;21), and t(15;17); (b) high‐risk: ‐5, 5q‐, ‐7, 3q abnormalities, t(8;16), t(6;9), t(6;11), t(6;21), t(10;11), complex karyotype (≥3 abnormalities), and acute megakaryocytic leukemia without t(1;22); and (c) IR: all the other karyotypes including normal. Patients in intermediate‐ or high‐risk group who were transplanted with either unrelated CB or matched unrelated BM/mobilized PB in their CR1 were included in this study. The projected OS and EFS rates were 74.9% and 71.1%, respectively, with a median follow‐up of 87.3 months after transplantation. The EFS was 70.1%, 80.7%, and 73.9% for CB, BM, and mobilized PB groups, respectively (P = 0.89), and 73.9% and 70.6% for IR and high‐risk groups (P = 0.76). The leading cause of death was relapse (n = 8), and only one patient died from non‐relapse cause. Unrelated donor HSCT seems a feasible approach for children with intermediate‐ or high‐risk AML in CR1. Relapse remains the leading cause of treatment failure among these patients. [ABSTRACT FROM AUTHOR]