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BACKGROUND: Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored. METHODS: A multi-institutional retrospective study was conducted to describe clinical characteristics, predictive factors, outcomes and late sequelae of pediatric reactivation/refractory LCH in Thailand. RESULTS: In all, 47 patients were studied, 25 (53.2%) patients had disease reactivation and 22 (46.8%) patients had refractory LCH. The median reactivation and refractory time were 1.59 and 0.33 years from diagnosis, respectively (p <0.001). The most common site of reactivation/refractory was the bone (n = 26, 55%), and 20 (42.6%) patients developed late sequelae. The 5-year overall survival (OS) was 76.1%. Patients with reactivation and refractory LCH performed similarly in 5-year OS (88% vs. 63%, p = 0.055). Prognostic factors associated with mortality were liver, spleen, hematopoietic system and lung reactivation (p <0.05). Lung reactivation was the only independent risk factor associated with the survival outcome (p = 0.002). CONCLUSIONS: The outcomes of pediatric patients between reactivation and refractory LCH in Thailand were similarly desirable and mortality was minimal although late sequelae may evolve. Pulmonary reactivation/refractory was an independent risk factor associated with survival.
Assuntos
Histiocitose de Células de Langerhans , Humanos , Histiocitose de Células de Langerhans/mortalidade , Histiocitose de Células de Langerhans/patologia , Masculino , Feminino , Estudos Retrospectivos , Criança , Prognóstico , Pré-Escolar , Tailândia/epidemiologia , Taxa de Sobrevida , Lactente , Seguimentos , Adolescente , Fatores de RiscoRESUMO
BACKGROUND: In Thailand, the national health care system and nationwide standard treatment protocols have evolved over time, potentially influencing the trends in the incidence and survival rates of childhood cancers. However, further investigations are required to comprehensively study these trends in Khon Kaen, Thailand. METHODS: Childhood cancer patients aged 0-14 years (n = 541) who were diagnosed with one of the five most common cancers between 2000 and 2019 from the population-based Khon Kaen Cancer Registry were enrolled. Descriptive statistics were used to analyse the demographic data, which are presented as numbers, percentages, means, and standard deviations. The trends in incidence between 2000 and 2019, including age-standardized incidence rates (ASRs) and annual percent changes (APCs), were analysed using the Joinpoint regression model. Survival analysis was performed for 5-year relative survival rates (RSRs) according to the Pohar Perme estimator and Kaplan-Meier survival curves. RESULTS: The ASRs of the overall top 5 childhood cancer groups were 67.96 and 106.12 per million person-years in 2000 and 2019, respectively. Overall, the APC significantly increased by 2.37% each year for both sexes. The overall 5-year RSRs were 60.5% for both sexes, 58.2% for males, and 63.9% for females. The highest 5-year RSR was for germ cell tumours (84.3%), whereas the lowest 5-year RSR was for neuroblastoma (29.1%). CONCLUSIONS: The incidence and survival rates of childhood cancers in Khon Kaen, Thailand, varied according to sex. The incidence trends increased over time, meanwhile, the relative survival rates rose to satisfactory levels and were comparable to those of other nations with similar financial status. The implementation of national health policies and adherence to national treatment guidelines have improved cancer diagnosis and treatment outcomes.
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Neoplasias , Sistema de Registros , Humanos , Tailândia/epidemiologia , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Incidência , Adolescente , Neoplasias/mortalidade , Neoplasias/epidemiologia , Recém-Nascido , Taxa de Sobrevida , Análise de SobrevidaRESUMO
Children with acute lymphoblastic leukaemia (ALL) are at risk for obesity and cardiometabolic diseases. To gain insight into body composition changes among children with ALL, we assessed quantitative computed tomography (QCT) data for specific body compartments (subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT], total adipose tissue [TAT], lean tissue [LT], LT/TAT and VAT/SAT at lumbar vertebrae L1 and L2) at diagnosis and at off-therapy for 189 children with ALL and evaluated associations between body mass index (BMI) Z-score and clinical characteristics. BMI Z-score correlated positively with SAT, VAT and TAT and negatively with LT/TAT and VAT/SAT. At off-therapy, BMI Z-score, SAT, VAT and TAT values were higher than at diagnosis, but LT, LT/TAT and VAT/SAT were lower. Patients aged ≥10 years at diagnosis had higher SAT, VAT and TAT and lower LT and LT/TAT than patients aged 2.0-9.9 years. Female patients had lower LT and LT/TAT than male patients. Black patients had less VAT than White patients. QCT analysis showed increases in adipose tissue and decreases in LT during ALL therapy when BMI Z-scores increased. Early dietary and physical therapy interventions should be considered, particularly for patients at risk for obesity.
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Composição Corporal , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Feminino , Criança , Tecido Adiposo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Índice de Massa Corporal , Obesidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagemRESUMO
BACKGROUND: Two types of rotavirus vaccines (RVs), Rotarix (RV1) and RotaTeq (RV5), were licensed as optional vaccines in 2012 and became part of the National Immunization Program (NIP) in the fiscal year 2020 in Thailand. The main objective was to evaluate the impact of rotavirus vaccines on the burden of acute diarrheal severity ranging from outpatient visits, diarrheal-related admission or deaths in the pre-NIP period (fiscal year 2015-2019) and in the fiscal year 2020. The minor objectives were assessed on the monthly admission rate, rotavirus vaccine coverage rate and rotavirus vaccine completed dose (RotaC). METHODS: Data regarding OPD, admission, and death cases under the Thailand National Health Coverage (NHC) from fiscal year 2015-2020, which were recorded as International Classification of Diseases and Related Health Problem 10th (ICD-10), were analyzed. RESULTS: The burden of diarrheal-related disease diminished after the rotavirus vaccine was introduced in the fiscal year 2020 when compared to the previous 5 fiscal years. The OPD visit rate decreased from 10.1 to 8.3 visits per 100 person-years (P < 0.001), or a 17.8% reduction (incidence rate ratio (IRR) = 0.82; 95% confidence interval (CI): 0.81 to 0.82). The admission rate significantly declined from 31.4 to 30.5 cases per 1,000 person-years, (P < 0.001), or a 2.9% reduction (IRR = 0.97; 95% CI: 0.96 to 0.98). The diarrheal-related mortality rate also subsided from 10.2 to 8.1 cases per 100,000 person-years (P 0.3), or a 20.0% reduction (IRR = 0.88; 95% CI: 0.50 to 1.22). The major population in both admissions and deaths was infants under 1 year of age (P < 0.001). Seasonality was seen as a constant bimodal pattern, with a significant decrease in monthly admissions after 6 months of rotavirus vaccine introduction to NIP (P < 0.001). RotaC was 37.4% in the first year of NIP. CONCLUSIONS: The rotavirus vaccine had a potential benefit for reducing the diarrheal disease burden, especially in infants under one year of age. Seasonality outbreaks of acute diarrhea subsided after the rotavirus vaccine was introduced. The RotaC was fairly low in the first year of the NIP. The quality of the rotavirus vaccine should be warranted. TRIAL REGISTRATION: Number TCTR20220120003 , date of registration: 20/01/2022, site: Thai Clinical Trials Registry.
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Diarreia , Infecções por Rotavirus , Vacinas contra Rotavirus , Pré-Escolar , Humanos , Lactente , Diarreia/epidemiologia , Diarreia/prevenção & controle , Programas de Imunização , Rotavirus , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , População do Sudeste Asiático , Tailândia/epidemiologia , Vacinação , Vacinas AtenuadasRESUMO
BACKGROUND: Low bone mineral density (BMD) is prevalent in individuals with ß-thalassemia and is associated with increased circulating dickkopf-1 concentration. These data are limited in α-thalassemia. Therefore, we aimed to determine the prevalence of low BMD and the association between BMD and serum dickkopf-1 in adolescents with non-deletional hemoglobin H disease, a form of α-thalassemia whose severity is comparable to ß-thalassemia intermedia. METHODOLOGY: The lumbar spine and total body BMD were measured and converted into height-adjusted z-scores. Low BMD was defined as BMD z-score ≤ -2. Participant blood was drawn for measurement of dickkopf-1 and bone turnover marker concentrations. RESULTS: Thirty-seven participants with non-deletional hemoglobin H disease (59% female, mean age 14.6 ± 3.2 years, 86% Tanner stage ≥2, 95% regularly transfused, 16% taking prednisolone) were included. Over one year prior to the study, mean average pretransfusion hemoglobin, ferritin and 25-hydroxyvitamin D concentrations were 8.8 ± 1.0 g/dL, and 958 ± 513 and 26 ± 6 ng/mL, respectively. When participants taking prednisolone were excluded, the prevalence of low BMD at the lumbar spine and total body was 42% and 17%, respectively. BMD at both sites was correlated positively with body mass index z-score, and negatively with dickkopf-1 (all p-values <0.05). There were no correlations among dickkopf-1, 25-hydroxyvitamin D, osteocalcin and C-telopeptide of type-I collagen. Multiple regression analysis showed dickkopf-1 inversely associated with total body BMD z-score adjusting for sex, bone age, body mass index, pre-transfusion hemoglobin, 25-hydroxyvitamin D, history of delayed puberty, type of iron chelator and prednisolone use (p-valueâ¯=â¯0.009). CONCLUSIONS: We demonstrated a high prevalence of low BMD in adolescents with non-deletional hemoglobin H disease. Moreover, dickkopf-1 inversely associated with total body BMD suggesting it may serve as a bone biomarker in this patient population.
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Doenças Ósseas Metabólicas , Talassemia alfa , Talassemia beta , Humanos , Feminino , Adolescente , Criança , Masculino , Densidade Óssea , Vértebras Lombares/diagnóstico por imagem , Hemoglobinas , PrednisolonaRESUMO
BACKGROUND: The incidence of acute diarrhea in Thai children under five years of age has increased over the last three decades. Even though mortality has significantly declined, the burden and cost of medical treatment are still high. Our objectives are to describe the burden and pattern of acute diarrhea cases that required admissions by Thai children under five years of age from 2015 to 2019. METHODS: Data regarding the admission of acute diarrhea cases of Thai children with Thailand National Health Coverage (NHC) under five years of age from 2015 to 2019, recorded as International Statistical Classification of Diseases and Related Health Problems, tenth Revision, Thai Modification (ICD-10-TM), were analyzed. RESULTS: The incidence trend of yearly acute diarrhea in children 0-5 years of age slightly increased from 33.36 cases per 1,000 population in 2010 to an average of 33.79 cases per 1,000 population/ year from 2015 to 2019 or approximately 0.43 cases per 1,000 population over the last decade while diarrhea-related mortality had a low, constant rate of 0.71 to 1.16 per 100,000 population per year. Two thirds of the mortality rate was observed in children under 1 year of age or 4.1 cases per 100,000 person-years in 5-year period (P < 0.01). The high cost of performing the medical treatment of approximately four hundred million baht per year. Seasonal variations demonstrated consistency with similar patterns during the cold and rainy seasons throughout the 5-year period. Regional distribution of the causative agent was also observed in Cholera, Typhoid, and Amoebiasis cases. A08: viral and other specified intestinal infections and A09: other gastroenteritis and colitis of infectious and unspecified origin were the two most common causes of diarrheal diseases. CONCLUSIONS: The incidence rate of acute diarrhea in Thai children under five years of age was higher while the mortality rate of acute diarrhea was lower than those in the past decade. A similar seasonal outbreak of acute diarrhea was seen during each examined year. The causative agent was not significant and was mainly unspecific. TRIAL REGISTRATION: Number TCTR20220117002, date of registration: 17/01/2022, site: Thai Clinical Trials Registry, URL http://www.thaiclinicaltrials.org/show/TCTR20220117002.
Assuntos
Diarreia , Gastroenterite , Pré-Escolar , Diarreia/epidemiologia , Diarreia/etiologia , Gastroenterite/complicações , Hospitalização , Humanos , Incidência , Lactente , Tailândia/epidemiologiaRESUMO
BACKGROUND: In 2013, the Thai Pediatric Oncology Group (ThaiPOG) introduced a national protocol in which high-dose chemotherapy plus stem cell rescue is performed without immunotherapy. METHODS: This study aimed to elucidate the outcomes of high-risk neuroblastoma (HR-NB) patients treated with the ThaiPOG protocol. This retrospective cohort review included 48 patients (30 males, 18 females) with a median age of 3 years (range, 8 months to 18 years) who were treated at 5 ThaiPOG treatment centers in Thailand in 2000-2018. RESULTS: Eight of the 48 patients showed MYCN amplification. Twenty-three patients (48%) received 131I-meta-iodobenzylguanidine prior to high-dose chemotherapy and stem cell rescue. The majority of patients achieved a complete or very good response prior to consolidation treatment. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.1% and 40.4%, respectively. Patients aged >2 years had a nonsignificantly higher mortality risk (hazard ratio [HR], 2.66; 95% confidence interval [CI], 0.92-7.68; P=0.07). The MYCN amplification group had lower OS and EFS rates than the MYCN nonamplification group, but the difference was not statistically significant (45% OS and 37.5% EFS vs. 33.3% OS and 16.6% EFS; P=0.67 and P=0.67, respectively). Cis-retinoic acid treatment for 12 months was a strong prognostic factor that could reduce mortality rates among HR-NB patients (HR, 0.27; 95% CI, 0.09-0.785; P=0.01). CONCLUSION: High-dose chemotherapy plus stem cell rescue followed by cis-retinoic acid for 12 months was well tolerated and could improve the survival rates of patients with HR-NB.
RESUMO
BACKGROUND: Neuroblastoma is the most common extracranial malignant solid tumor during childhood. Despite intensified treatment, patients with high-risk neuroblastoma (HR-NBL) still carry a dismal prognosis. The Thai Pediatric Oncology Group (ThaiPOG) proposed the use of a multimodality treatment to improve outcomes of HR-NBL in non-immunotherapy settings. METHODS: Patients with HR-NBL undergoing ThaiPOG protocols (ThaiPOG-NB-13HR or -18HR) between 2013 and 2019 were retrospectively reviewed. Patient demographic data, treatment modalities, outcomes, and prognostic factors were evaluated and analyzed. RESULTS: A total of 183 patients with HR-NBL undergoing a topotecan containing induction regimen were enrolled in this study. During the consolidation phase (n = 169), 116 patients (68.6%) received conventional chemotherapy, while 53 patients (31.4%) underwent hematopoietic stem cell transplantation (HSCT). The 5-year overall survival (OS) and event-free survival (EFS) were 41.2% and 22.8%, respectively. Patients who underwent HSCT had more superior 5-year EFS (36%) than those who received chemotherapy (17.1%) (p = .041), although they both performed similarly in 5-year OS (48.7% vs. 39.8%, p = .17). The variation of survival outcomes was observed depending on the number of treatment modalities. HSCT combined with metaiodobenzylguanidine (MIBG) treatment and maintenance with 13-cis-retinoic acid (cis-RA) demonstrated a desirable 5-year OS and EFS of 65.6% and 58.3%, respectively. Poorly or undifferentiated tumor histology and cis-RA administration were independent factors associated with relapse and survival outcomes, respectively (p < .05). CONCLUSION: A combination of HSCT and cis-RA successfully improved the outcomes of patients with HR-NBL in immunotherapy inaccessible settings.
Assuntos
Recidiva Local de Neoplasia , Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Humanos , Lactente , Isotretinoína , Recidiva Local de Neoplasia/patologia , Neuroblastoma/patologia , Estudos Retrospectivos , Tailândia , Resultado do TratamentoRESUMO
Langerhans cell histiocytosis (LCH) is a rare disease across all age groups and is characterized by various degrees of severity and organ system involvement. A multi-institutional retrospective study of pediatric patients with LCH treated between 1999 and 2018 at five pediatric oncology centers was conducted to describe the clinical characteristics, prognostic factors, and outcomes of LCH and to validate screening tools for organ system involvement in pediatric LCH in Thailand. A total of 127 patients with a median age of 2.7 years were studied. The single-to-multisystem (MS) LCH ratio was 1:1. Forty-seven patients (71%) with MS-LCH had risk-organ involvement (RO +), whereas 19 (29%) patients had no risk-organ involvement (RO -). The 5-year overall and event-free survival rates were 91.3% and 73.6%, respectively, which were comparable to those in developed countries. Prognostic factors included age < 2 years, RO + MS-LCH, and number of RO + . Abnormal complete blood count was a highly sensitive indicator of bone marrow involvement. Plain radiography is an appropriate screening tool to detect bone involvement.
Assuntos
Histiocitose de Células de Langerhans , Neoplasias , Criança , Pré-Escolar , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Lactente , Intervalo Livre de Progressão , Estudos Retrospectivos , Tailândia/epidemiologiaRESUMO
OBJECTIVE: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma. METHODS: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model. RESULT: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22-1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 µM (OR 1.22; 95% CI 1.19-1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07-1.12; P<0.001). CONCLUSION: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.
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Antineoplásicos/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Osteossarcoma/tratamento farmacológico , Adolescente , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metotrexato/efeitos adversos , Náusea/induzido quimicamente , Náusea/epidemiologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Razão de Chances , Estado de Hidratação do Organismo/efeitos dos fármacos , Prevalência , Estudos Retrospectivos , Tailândia/epidemiologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Vômito/induzido quimicamente , Vômito/epidemiologiaRESUMO
6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15∗3 and NUDT15∗2 genotypes were at a 10-15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15∗3 and NUDT15∗2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.
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Mercaptopurina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Povo Asiático , Criança , Genótipo , Humanos , Mercaptopurina/efeitos adversos , Mercaptopurina/metabolismo , Metiltransferases/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted. Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author's name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed. Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11-18.35) and 16.35 (95% CI 10.20-26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65-24.27) and early neutropenia (OR 15.85; 95% CI 8.80-28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99-708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia. Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary.