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1.
Article in English | WPRIM | ID: wpr-915510

ABSTRACT

Background@#Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB. @*Methods@#The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues. @*Results@#A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system. @*Conclusion@#The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

2.
Article in English | WPRIM | ID: wpr-913836

ABSTRACT

Purpose@#We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. @*Materials and Methods@#The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. @*Results@#An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. @*Conclusion@#In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

3.
Article in English | WPRIM | ID: wpr-903140

ABSTRACT

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

4.
Article in English | WPRIM | ID: wpr-900012

ABSTRACT

Background@#The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia. @*Methods@#Medical records of patients with acute leukemia who received CBT were retrospectively reviewed. @*Results@#A total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m 2 were named as the TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis (P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group (P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively (P = 0.017). @*Conclusion@#Patients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia.

5.
Article in English | WPRIM | ID: wpr-895436

ABSTRACT

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

6.
Article in English | WPRIM | ID: wpr-892308

ABSTRACT

Background@#The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia. @*Methods@#Medical records of patients with acute leukemia who received CBT were retrospectively reviewed. @*Results@#A total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m 2 were named as the TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis (P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group (P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively (P = 0.017). @*Conclusion@#Patients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia.

7.
Article in English | WPRIM | ID: wpr-874161

ABSTRACT

Background@#We developed an assay to measure DNA-incorporated 6-thioguanine (DNATG) and validated its clinical applicability in Korean pediatric patients with acute lymphoblastic leukemia (ALL) in order to improve individualized thiopurine treatment and reduce the life-threatening cytotoxicity. @*Methods@#The DNA-TG assay was developed based on liquid chromatography-tandem mass spectrometry, with isotope-labeled TG-d3 and guanine-d3 as internal standards.This method was applied to 257 samples of pediatric ALL patients. The DNA-TG level was compared with erythrocyte TG nucleotide (RBC-TGN) level in relation to the TPMT and NUDT15 genotypes, which affect thiopurine metabolism, using Spearman’s rank test and repeated measure ANOVA. @*Results@#For DNA-TG quantification, a linearity range of 10.0-5,000.0 fmol TG/µg DNA;bias for accuracy of –10.4% –3.5%; coefficient of variation for intra- and inter-day precision of 3.4% and 5.8% at 80 fmol TG/µg DNA and of 4.9% and 5.3% at 800 fmol TG/µg DNA, respectively; and recovery of 85.7%–116.2% were achieved without matrix effects or carry-over. The median DNA-TG level in the 257 samples was 106.0 fmol TG/µg DNA (interquartile range, 75.8–150.9). There was a strong correlation between DNA-TG and RBC-TGN levels (ρ = 0.68,ρ < 0.0001). The DNA-TG/RBC-TGN ratio was significantly higher in NUDT15 intermediate metabolizers (*1/*2 and *1/*3) than in patients with wildtype alleles (ρ < 0.0001). @*Conclusions@#This simple and sensitive method for measuring DNA-TG level can improve therapeutic drug monitoring for thiopurine treatment.

8.
Article in English | WPRIM | ID: wpr-899708

ABSTRACT

Background@#This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. @*Methods@#Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. @*Results@#Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. @*Conclusion@#This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.

9.
Article in English | WPRIM | ID: wpr-892004

ABSTRACT

Background@#This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. @*Methods@#Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. @*Results@#Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. @*Conclusion@#This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.

10.
Article | WPRIM | ID: wpr-832104

ABSTRACT

Hereditary spherocytosis (HS) is the most common inherited red cell membrane disorder. Its main laboratory finding is anemia with reticulocytosis. However, in the case of an aplastic crisis, there may be no reticulocytosis, making the diagnosis of HS difficult. We present the case of a 4-year-old boy who initially presented with persistent fever and sore throat. His 8-year old brother also had anemia of unknown etiology, and his father had a history of splenectomy in his 20s. Physical examination revealed anemic conjunctivae and hepatosplenomegaly, and laboratory findings showed anemia with decreased reticulocyte count and elevated ferritin and lactate dehydrogenase levels. A peripheral blood smear showed microcytic hypochromic anemia with severe poikilocytosis (spherocytes, acanthocytes, schistocytes), and bone marrow examination revealed decreased erythroid cells and increased hemophagocytosis. Increased osmotic fragility was observed, and parvovirus B19 was detected using polymerase chain reaction. Hence, we established the diagnosis of hereditary spherocytosis manifested as an aplastic crisis caused by parvovirus B19 infection

11.
Article in English | WPRIM | ID: wpr-831569

ABSTRACT

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, highrisk, 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.

12.
Article in English | WPRIM | ID: wpr-765092

ABSTRACT

BACKGROUND: Neurotrophin-3 (NT-3), a member of the NT family, has only been considered an ancillary compound that provides anti-apoptotic benefits by inactivating tropomyosin receptor kinase C (TrkC)-induced apoptotic signals. However, little is known about the clinical relevance of NT-3 expression itself in neuroblastoma. The purpose of this study was to assess NT-3 expression in patients with neuroblastoma and its relevance to clinicopathologic findings and treatment outcomes. METHODS: In this study, expression of NT-3 and TrkC was analyzed using immunohistochemistry in 240 patients with newly diagnosed neuroblastoma. RESULTS: The results of the study revealed that NT-3 expression was associated with older age at diagnosis, localized tumors, and more differentiated tumors but was not associated with early treatment response (degree of residual tumor volume after three cycles of chemotherapy) and progression-free survival (PFS). However, when analysis was confined to patients with MYCN amplified tumors, NT-3 expression was associated with better early treatment response with borderline significance (P = 0.092) and higher PFS (86.9% vs. 58.2%; P = 0.044). In multivariate analysis in patients with MYCN amplified tumors, NT-3 was independent prognostic factor (hazard ratio, 0.246; 95% confidence interval, 0.061–0.997; P = 0.050). In another subgroup analysis, the early treatment response was better if NT-3 was expressed in patients without TrkC expression (P = 0.053) while it was poorer in patients with TrkC expression (P = 0.023). CONCLUSION: This study suggests that NT-3 expression in neuroblastoma has its own clinical significance independent of TrkC expression, and its prognostic significance differs depending on the status of MYCN amplification and/or TrkC expression.


Subject(s)
Diagnosis , Disease-Free Survival , Humans , Immunohistochemistry , Multivariate Analysis , Neoplasm, Residual , Neuroblastoma , Phosphotransferases , Tropomyosin
13.
Article in English | WPRIM | ID: wpr-717690

ABSTRACT

BACKGROUND: By estimating the survival rates and exploring prognostic factors in pediatric patients with relapsed or progressed solid tumors, our purpose was to generate background data for future studies. METHODS: We reviewed the medical records of 258 patients with solid tumors who experienced relapse/progression and received subsequent salvage treatment between 1996 and 2016. RESULTS: A total of 60 patients remained progression-free during first-line salvage treatment, while the remaining 198 patients experienced relapse/progression again; 149 underwent second-line salvage treatment. A total of 76 patients underwent high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), and 44 patients received allogeneic SCT. The 10-year progression-free survival (PFS) and overall survival (OS) from relapse/progression were 18.4% ± 2.7% and 24.5% ± 3.0%, respectively. Survival rates were relatively higher in patients with anaplastic ependymoma, initially non-high-risk neuroblastoma, osteosarcoma, Wilms tumor and retinoblastoma. A multivariate analysis showed that relapse/progression during initial treatment, metastatic relapse/progression, and impossible debulking surgery were independent poor prognostic factors for both PFS and OS. Patients who exhibited a complete response or partial response during conventional salvage treatment showed significantly higher survival after SCT than those with stable disease or progressive disease (10-year OS: 54.8% ± 7.0% vs. 7.0% ± 3.5%, P < 0.001). CONCLUSION: The prognosis of relapsed/progressed pediatric solid tumors still remains unsatisfactory. New, effective treatment strategies are needed to overcome limitations of current approaches. Hopefully, the background data generated herein will be used in future clinical trials involving patients with relapsed/progressed solid tumors.


Subject(s)
Adolescent , Child , Disease-Free Survival , Drug Therapy , Ependymoma , Humans , Medical Records , Multivariate Analysis , Neuroblastoma , Osteosarcoma , Prognosis , Recurrence , Retinoblastoma , Salvage Therapy , Stem Cell Transplantation , Survival Rate , Wilms Tumor
14.
Blood Research ; : 242-248, 2016.
Article in English | WPRIM | ID: wpr-167172

ABSTRACT

BACKGROUND: This retrospective study aimed to characterize and analyze the outcome of therapy-related myeloid neoplasms (t-MNs) in children and adolescents. METHODS: The medical records of 16 patients under 21 years of age at the time of t-MN diagnosis were reviewed. RESULTS: The median patient age was 11.5 years (range, 1.6–20.4 yr). Twelve patients had therapy-related acute myeloid leukemia, 3 patients had myelodysplastic syndrome, and 1 patient had chronic myelomonocytic leukemia. The median latency period was 29 months (range, 11–68 mo). Fourteen patients had cytogenetic aberrations, 8 of whom had an 11q23 abnormality. Of the 13 patients treated with curative intent, 12 patients received myeloid-type induction therapy that led to complete remission (CR) in 8 patients. Nine patients underwent allogeneic transplantation; 4 patients did not undergo transplantation due to chemotherapy-related toxic death (N=3) or parental refusal (N=1). The 5-year overall survival and event-free survival of the 13 patients treated with a curative intent were 46.2% and 30.8%, respectively. For the 9 patients who underwent allogeneic transplantation, the 5-year event-free survival was 66.7%. CONCLUSION: A significant proportion of young patients with t-MNs can experience long-term survival, and allogeneic transplantation plays a key role for attaining cure in these patients.


Subject(s)
Adolescent , Child , Chromosome Aberrations , Diagnosis , Disease-Free Survival , Humans , Latency Period, Psychological , Leukemia, Myeloid, Acute , Leukemia, Myelomonocytic, Chronic , Medical Records , Myelodysplastic Syndromes , Parents , Retrospective Studies , Transplantation, Homologous
15.
Korean Journal of Pediatrics ; : S103-S106, 2016.
Article in English | WPRIM | ID: wpr-201849

ABSTRACT

Bartter syndrome (BS) is an inherited renal tubular disorder characterized by low or normal blood pressure, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism. Type III BS is caused by loss-of-function mutations in CLCNKB encoding basolateral ClC-Kb. The clinical phenotype of patients with CLCNKB mutations has been known to be highly variable, and cases that are difficult to categorize as type III BS or other hereditary tubulopathies, such as Gitelman syndrome, have been rarely reported. We report a case of a 10-year-old Korean boy with atypical clinical findings caused by a novel CLCNKB mutation. The boy showed intermittent muscle cramps with laboratory findings of hypokalemia, severe hypomagnesemia, and nephrocalcinosis. These findings were not fully compatible with those observed in cases of BS or Gitelman syndrome. The CLCNKB mutation analysis revealed a heterozygous c.139G>A transition in exon 13 [p.Gly(GGG)465Glu(GAG)]. This change is not a known mutation; however, the clinical findings and in silico prediction results indicated that it is the underlying cause of his presentation.


Subject(s)
Alkalosis , Bartter Syndrome , Blood Pressure , Child , Computer Simulation , Exons , Gitelman Syndrome , Humans , Hyperaldosteronism , Hypokalemia , Male , Muscle Cramp , Nephrocalcinosis , Phenotype
16.
Article in English | WPRIM | ID: wpr-25408

ABSTRACT

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) has been known to greatly influence the survival rate of patients with liver cirrhosis. However, the factors that affect the survival rate in patients with SBP need to be clarified. METHODS: This study enrolled 95 liver cirrhosis patients diagnosed with SBP. The laboratory findings of their serum and ascitic fluid were examined and the characteristics of the isolated microorganisms in their peritoneal fluid were analyzed. RESULTS: The proportion of patients with culture-positive SBP was 41.1%, and 47 microorganisms were isolated from the ascitic fluid. The proportions of cultured bacteria that were Gram negative and Gram positive were 57.4% and 40.4%, respectively. The proportions of Escherichia coli, Klebsiella species, and Streptococcus species were 25.5%, 19.1%, and 19.1%, respectively. Enterococcus species represented 12.8% of the microorganisms cultured. The overall survival rates at 6, 12, and 24 months were 44.5%, 37.4%, and 32.2%, respectively. There was no relationship between the bacterial factors and the survival rate in SBP. Multivariate analysis revealed that the presence of hepatocellular carcinoma (HCC; P=0.001), higher serum bilirubin levels (> or =3 mg/dL, P=0.002), a prolonged serum prothrombin time (i.e., international normalized ratio >2.3, P1.3 mg/dL, P<0.001), and lower glucose levels in the ascitic fluid (<50 mg/dL, P<0.001) were independent predictive factors of overall survival rate. CONCLUSIONS: HCC, higher serum bilirubin levels, a prolonged serum prothrombin time, renal dysfunction, and lower ascitic glucose levels are associated with higher mortality rates in cirrhotic patients with SBP.


Subject(s)
Adult , Aged , Anti-Bacterial Agents/therapeutic use , Ascitic Fluid/metabolism , Bilirubin/blood , Carcinoma, Hepatocellular/complications , Creatinine/blood , Female , Glucose/analysis , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Humans , Liver Cirrhosis/complications , Liver Neoplasms/complications , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Peritonitis/complications , Prognosis , Prothrombin Time , Survival Rate
18.
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