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1.
J Oncol Pharm Pract ; 29(2): 319-325, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34931912

RESUMO

INTRODUCTION: Children with cancer may be one of the most vulnerable groups to drug-related adverse events because they possess characteristics of patients with cancer as well as pediatric patients. To evaluate the clinical and economic impact of pharmacists' intervention on the care of pediatric hematology and oncology patients in the inpatient and outpatient settings of a children's hospital. METHODS: The pharmacist-intervention records from 2017 were retrospectively reviewed. Intervention rate, type of drug-related problems, acceptance rate, and frequently involved drugs in pharmacist interventions were analyzed. One physician and one pharmacist evaluated the clinical significance of each intervention. A cost-benefit analysis was conducted from hospital and patient perspective. The benefit from cost savings by reducing the number of prescribed drugs that are disposed was estimated as the benefit from hospital perspective. The benefit from cost avoidance based on the potential to avoid an adverse drug event (ADE) was estimated as the benefit from patient perspective. The cost of reviewing prescriptions was estimated based on the pharmacists' salary and the time involved. RESULTS: In 2017, 2361 interventions were performed in 381 pediatric patients with cancer. The acceptance rate was 97.2%. More than half of the interventions were regarded as clinically "significant" (58.8%) and "very significant" (14.6%). The cost-benefit of US$28,705 was determined from hospital perspective, with a cost-benefit ratio of 1.45:1. The cost-benefit of US$35,611 was calculated from patient perspective, with a cost-benefit ratio of 1.55:1. CONCLUSIONS: Pharmacists' intervention in the care of hematology and oncology pediatric patients was effective in preventing clinically significant ADEs and had a positive economic impact on the health-care budget from both hospital and patient perspective.


Assuntos
Hematologia , Neoplasias , Serviço de Farmácia Hospitalar , Humanos , Criança , Farmacêuticos , Estudos Retrospectivos , Neoplasias/tratamento farmacológico , Pacientes Internados
2.
J Korean Med Sci ; 38(30): e234, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37527911

RESUMO

BACKGROUND: This study characterized coronavirus disease 2019 (COVID-19) vaccination behavior in the Korean general population using cluster analysis and explored related psychological factors. METHODS: We categorized 1,500 individuals based on their attitudes toward COVID-19 vaccination using hierarchical clustering and identified their level of vaccine acceptance. We examined the associations between vaccine acceptance and behavioral and psychological characteristics. RESULTS: Clustering revealed three groups according to vaccine acceptance: 'totally accepting' (n = 354, 23.6%), 'somewhat accepting' (n = 523, 34.9%), and 'reluctant' (n = 623, 41.5%). Approximately 60% of all participants who belonged to the 'totally accepting' and 'somewhat accepting' groups were willing to receive a COVID-19 vaccine despite concerns about its side effects. High vaccine acceptance was associated with older age, regular influenza vaccination, and trust in formal sources of information. Participants with high vaccine acceptance had higher levels of gratitude, extraversion, agreeableness, and conscientiousness, and lower levels of depression, anxiety, and neuroticism. CONCLUSIONS: People weighed the benefits of COVID-19 vaccination against the risk of side effects when deciding to receive the COVID-19 vaccine. Our findings also indicate that this vaccination behavior may be affected by coping mechanisms and psychological factors.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Vacinação , Personalidade , República da Coreia
3.
Psychol Med ; 51(6): 964-974, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31907104

RESUMO

BACKGROUND: To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS). METHODS: Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5-12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M). RESULTS: Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63-2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline. CONCLUSIONS: Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/psicologia , Depressão/epidemiologia , Depressão/psicologia , Adulto , Idoso , Depressão/diagnóstico , Depressão/tratamento farmacológico , Escitalopram/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
4.
J Pediatr Hematol Oncol ; 43(2): e280-e283, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32251153

RESUMO

The therapeutic approach for relapsed/refractory acute lymphoblastic leukemia (ALL) remains to be a challenge. The patient was diagnosed as B-cell ALL at 6 months of age and relapsed for the second time following repeat allogeneic hematopoietic stem cell transplantation (one after first complete remission [CR1] and the other after CR2). During blinatumomab monotherapy, he developed an extramedullary relapse. Finally, the combined therapy with clofarabine, donor lymphocyte infusion, and blinatumomab induced CR of the bone marrow and extramedullary relapse. Unfortunately, the patient developed central nervous system relapse, however, this case showed a promising potential for combination therapy with clofarabine, donor lymphocyte infusion, and blinatumomab in relapsed/refractory B-cell ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Transfusão de Linfócitos/métodos , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Anticorpos Biespecíficos/administração & dosagem , Doadores de Sangue , Clofarabina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Estudos Retrospectivos
5.
J Pediatr Hematol Oncol ; 43(7): e1015-e1019, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33769384

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of diseases with abnormal proliferation of lymphoid tissue and classical Hodgkin lymphoma (CHL) type PTLD is a very rare subtype. We describe a successfully diagnosed and treated CHL-PTLD stage IV pediatric patient, 8 years after liver transplantation. The patient was treated with standard CHL (Children's Cancer Group 5942 group 3) chemotherapy, rituximab and reduction of immunosuppressant. The patient remains in complete remission after 3 years with stable graft function. To our best knowledge, this is the first pediatric case report of a successfully treated stage IV CHL-PTLD after a liver transplant.


Assuntos
Atresia Biliar/cirurgia , Doença de Hodgkin/patologia , Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/patologia , Complicações Pós-Operatórias/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atresia Biliar/patologia , Criança , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/etiologia , Humanos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Prognóstico
7.
Pediatr Hematol Oncol ; 38(4): 378-384, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33653209

RESUMO

Imatinib is a BCR-ABL tyrosine kinase inhibitor used for the treatment of a variety of diseases including Philadelphia chromosome positive (Ph+) leukemia. We report a 15 year old male patient presenting with symptomatic acute intracerebral hemorrhage (ICH) in midbrain while on imatinib more than three years after completion of therapy for Ph + B-ALL. The patient denied recent trauma history and consumption of other medication. Laboratory findings did not show any signs of relapse, coagulopathy nor thrombocytopenia. Under the impression of imatinib related ICH, imatinib was discontinued and with conservative management the patient recovered without neurologic sequalae. This case demonstrates the first pediatric case of spontaneous ICH as a rare complication of imatinib.


Assuntos
Antineoplásicos/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Mesilato de Imatinib/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/uso terapêutico , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações
8.
BMC Cancer ; 20(1): 979, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036578

RESUMO

BACKGROUND: Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy. METHODS: We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children's Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients' choice. RESULTS: The median age at diagnosis was 11.9 (range, 3.8-25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p < 0.001) and OS (77.9 ± 9.8%, p = 0.024) rates compared to other HR patients who were not pathologically diagnosed or were confirmed as germinoma with elevated tumor markers. All mortalities were related to disease progression or secondary malignancy. CONCLUSION: The strategy of treating CNS GCTs with upfront chemotherapy according to risk groups resulted in good clinical outcomes and acceptable relapse incidence. However, further modification in the definition of the HR group is needed to reduce long-term complications.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/radioterapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Pediatr Blood Cancer ; 67(3): e28101, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793213

RESUMO

BACKGROUND: Cytomegalovirus (CMV) disease is underrecognized in children with retinoblastoma. This study investigated rates of CMV infection and disease in this specific population receiving chemotherapy. METHODS: From a cohort of 164 patients with retinoblastoma diagnosed from 2011 to 2018, 107 patients were evaluated for CMV infection determined by antigenemia assay or real-time PCR. Preemptive CMV screening was implemented in 2013. CMV disease was diagnosed by tissue biopsy, culture, or ophthalmic examination. RESULTS: Thirty-seven and 70 patients before and after the screening strategy, respectively, were included. Before screening, 10/37 (27%) were diagnosed with CMV infection during chemotherapy. Among them, 5 (50%) developed CMV disease (hepatitis, pneumonia, and retinitis) and one patient died of CMV pneumonia. During screening, 18/70 (26%) were documented with 36 episodes of CMV infection and 9 patients received 25 preemptive antiviral therapies. Age at chemotherapy tended to be younger in patients with CMV infection, and fewer were seronegative prior to chemotherapy. Patients who started chemotherapy at <12 months of age received preemptive therapies significantly more often than those started at ≥12 months. Two (11%) out of 18 patients with CMV infection developed CMV retinitis and colitis, and there were no fatal cases. Preemptive therapy along with active CMV screening significantly reduced the risk of developing CMV disease, from 14% to 2.9% (P = 0.047). CONCLUSIONS: Children with retinoblastoma can experience significant morbidity and even mortality from CMV infection during chemotherapy in Korea. Preemptive screening and appropriate antiviral therapy can reduce the development of CMV disease and subsequent mortality.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Programas de Rastreamento/estatística & dados numéricos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antivirais/uso terapêutico , Pré-Escolar , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , República da Coreia/epidemiologia , Neoplasias da Retina/patologia , Neoplasias da Retina/virologia , Retinoblastoma/patologia , Retinoblastoma/virologia , Estudos Retrospectivos
10.
J Pediatr Hematol Oncol ; 42(6): e488-e490, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-30951024

RESUMO

Wilms tumor is the most common renal malignancy in children. Most of Wilms tumor recurrences occur within 2 years of the first diagnosis. Relapse after 5 years after the first diagnosis is called "late recurrence" and is rare in Wilms tumor. There are few case reports or small series of late recurrence of Wilms tumor. Because of the rarity of late recurrence of Wilms tumor, there is no clear guideline for its management. We describe a case of late recurrence of Wilms tumor as a remote metastasis in the lung at 18 years after the first diagnosis and 17 years after the second remission, which was achieved by radiotherapy and high-dose chemotherapy with autologous stem cell rescue. After late recurrence, the patient was treated by surgery and adjuvant chemotherapy, and remained disease-free for 11 months. Several very late recurrences of Wilms tumor in the literature are reviewed.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias Renais/terapia , Recidiva Local de Neoplasia/terapia , Procedimentos Cirúrgicos Operatórios/métodos , Tumor de Wilms/terapia , Adolescente , Pré-Escolar , Terapia Combinada , Humanos , Neoplasias Renais/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Prognóstico , Tumor de Wilms/patologia
12.
J Korean Med Sci ; 35(33): e279, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32830468

RESUMO

BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.


Assuntos
Anemia Hemolítica Congênita/epidemiologia , Adolescente , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/epidemiologia , Criança , Pré-Escolar , Feminino , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Hemoglobinas/genética , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Polimorfismo Genético , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Erros Inatos do Metabolismo dos Piruvatos/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários
13.
J Korean Med Sci ; 35(46): e393, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33258329

RESUMO

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.


Assuntos
Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Antineoplásicos/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Doenças do Sistema Endócrino/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Lactente , Recém-Nascido , Masculino , República da Coreia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adulto Jovem
14.
J Pediatr ; 208: 243-250.e3, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30871796

RESUMO

OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria. STUDY DESIGN: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria. Impaired renal function of estimated glomerular filtration rate less than 90 mL/minute/1.73 m2 and development of proteinuria of cancer survivors were also assessed. RESULTS: This study included 1868 patients who were diagnosed with cancer at a median age of 7.9 years. During the course of treatment, 983 patients (52.6%) developed 1864 episodes of AKI, and the cumulative incidence at 2 weeks, 3 months, and 1 year after diagnosis was 28.9%, 39.6%, and 53.6%, respectively. The 1-year cumulative incidence was the highest in patients with acute myeloid leukemias (88.4%). In all, 6.1% of patients had more than 4 episodes of AKI and 11.8% of patients had stage 3 AKI. Among the 1096 childhood cancer survivors, 22.6% were found to have impaired renal function. A greater number of AKI episodes (≥4 times) and nephrectomy were independent risk factors of impaired renal function. Also, 8.2% of the survivors developed proteinuria among 742 childhood cancer survivors. CONCLUSIONS: A large percentage of children with cancer experience AKI during the course of treatment, and AKI is associated with impaired long-term renal function.


Assuntos
Injúria Renal Aguda/complicações , Neoplasias Encefálicas/complicações , Leucemia Mieloide Aguda/complicações , Injúria Renal Aguda/epidemiologia , Neoplasias Encefálicas/epidemiologia , Sobreviventes de Câncer , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/epidemiologia , Linfoma/complicações , Masculino , Nefrectomia , Proteinúria/complicações , Proteinúria/epidemiologia , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
Ther Drug Monit ; 41(1): 75-85, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30507626

RESUMO

BACKGROUND: Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP). METHODS: RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated. RESULTS: The imprecision coefficient of variations of 6TG and 6MMP were 5.7%-8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 10 RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 10 RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Eritrócitos/efeitos dos fármacos , Nucleotídeos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Tioguanina/farmacocinética , Tioguanina/uso terapêutico , Adolescente , Antimetabólitos Antineoplásicos/sangue , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Mercaptopurina/análogos & derivados , Mercaptopurina/sangue , Mercaptopurina/metabolismo , Nucleotídeos/sangue , Nucleotídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Espectrometria de Massas em Tandem/métodos , Tioguanina/sangue
16.
Transpl Infect Dis ; 21(6): e13182, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556214

RESUMO

BACKGROUND: The efficacy of preemptive treatment containing rituximab to prevent post-transplant lymphoproliferative disease (PTLD) in children has not yet been fully elucidated. METHODS: We analyzed 19 pediatric patients who developed high Epstein-Barr virus (EBV) DNAemia (EBV viral load of greater than 40 000 copies/mL) after allogeneic hematopoietic stem cell transplantation (HSCT) and were preemptively administered rituximab. Rituximab was intravenously injected at a dose of 375 mg/m2 once the EBV viral load was greater than 40 000 copies/mL. RESULTS: In all 19 patients, EBV DNAemia was eradicated after a median of 9 days (range, 3-20 days), and PTLD did not occur. One patient had transient fever, and four patients did not fully recover B cell counts after transplantation. We suggested that delayed B cell recovery was caused by chronic graft-versus-host disease (GVHD) related drugs, not rituximab administration. And there were no other infection-related side effects. CONCLUSIONS: In conclusion, preemptive therapy containing rituximab is expected to reduce the incidence of PTLD after HSCT and improve post-transplantation outcomes in children.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/prevenção & controle , Rituximab/administração & dosagem , Adolescente , Criança , Pré-Escolar , DNA Viral/isolamento & purificação , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Humanos , Imunossupressores/efeitos adversos , Incidência , Lactente , Injeções Intravenosas , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/virologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
17.
J Pediatr Hematol Oncol ; 41(5): e336-e337, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29889803

RESUMO

Epstein-Barr virus (EBV)-positive aggressive natural killer-cell leukemia (ANKL) is a rare malignancy of mature natural killer cells, with a very poor survival rate. Patients have a rapidly declining clinical course and a poor prognosis, with a median survival of only a few months. Herein, we describe a 16-year-old boy who was diagnosed with EBV-positive ANKL and successfully treated using combination chemotherapy and a subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT). The patient is disease free 4 years and 9 months after alloHSCT. Thus, combination chemotherapy followed by alloHSCT seems to be a promising therapeutic option for EBV-positive ANKL.


Assuntos
Terapia Combinada/métodos , Herpesvirus Humano 4 , Leucemia Linfocítica Granular Grande/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Linfocítica Granular Grande/virologia , Masculino , Transplante Homólogo/métodos
18.
J Thromb Thrombolysis ; 47(4): 558-565, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30666552

RESUMO

Thromboembolism (TE) is a major cause of morbidity and mortality in adult cancer patients; however, there is a lack of sufficient knowledge on TE in pediatric cancer patients. We aimed to determine the epidemiology of TE in Korean children with cancer. Between January 2000 and July 2015, we retrospectively analyzed pediatric patients newly diagnosed with cancer at six tertiary hospitals in Korea. Of 3611 children with cancer, 33 (0.91%) had TE. A higher number of patients with acute lymphoblastic leukemia (n = 13), brain tumors (n = 6), lymphoma (n = 4), and bone/soft tissue sarcomas (n = 5) tended to develop TE. The male/female ratio was 17/16, and the median age at TE diagnosis was 10 years and 2 months. TE was detected a median of 2 months after cancer diagnosis. Symptoms including pain and swelling were present in 18 of the 33 patients. In terms of location, three intracerebral, 23 upper venous, six lower venous and one combined upper and lower venous system TEs were observed. Additional risk factors for TE included central venous catheter (CVC) use in 12 patients, steroid and/or L-asparaginase use in nine, and CVC and steroid and/or L-asparaginase use in seven. The TE incidence rate was quite low among Korean children with cancer, but higher than in the general pediatric population and among children hospitalized for diseases other than cancer. Further investigation of a larger pool of patients is warranted to determine the most effective strategies to prevent and treat TE in Korean children with cancer.


Assuntos
Neoplasias Encefálicas/epidemiologia , Linfoma/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Tromboembolia/epidemiologia , Adolescente , Asparaginase/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Linfoma/tratamento farmacológico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Esteroides/administração & dosagem , Tromboembolia/etiologia
19.
Int J Clin Oncol ; 24(12): 1515-1525, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31352632

RESUMO

BACKGROUND: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors. METHODS: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. RESULTS: Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively. CONCLUSIONS: Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Transplante de Células-Tronco/métodos , Adolescente , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Melfalan/administração & dosagem , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Taxa de Sobrevida , Tiotepa/administração & dosagem , Topotecan/administração & dosagem , Transplante Autólogo/efeitos adversos , Transplante Autólogo/mortalidade , Resultado do Tratamento
20.
J Korean Med Sci ; 34(30): e203, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31373185

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/terapia , Viremia/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Transplante Homólogo , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
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