Hiperglicemia secundária ao tratamento da Leucemia Linfocítica Aguda em Pediatria, suas consequências e comparação de sua incidência entre os protocolos GBTLI 2009 e BFM 95 e 2002
Data
2022-07-15
Autores
Silva, Lívia Cristina Oliveira e 
Orientadores
Spinola-Castro, Angela Maria
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Identificar fatores de risco para hiperglicemia durante o tratamento da Leucemia Linfocítica Aguda (LLA) em pediatria e avaliar sua associação com eventos de gravidade. Comparar a incidência de hiperglicemia entre os pacientes submetidos aos protocolos de tratamento GBTLI-2009 e BFM 95 e 2002. Métodos: Foi realizada coleta de dados de um banco anonimizado incluindo os 188 pacientes pediátricos tratados por LLA no Instituto de Oncologia Pediátrica da Universidade Federal de São Paulo (IOP/UNIFESP) no período de 2004 a 2017. Analisou-se o efeito do sexo, idade, etnia, história familiar de diabetes, puberdade, estado nutricional, linhagem celular da LLA, cromossomo Philadelphia e síndrome de Down na ocorrência de hiperglicemia através de modelos de regressão logística uni e multivariada. O efeito da hiperglicemia como fator preditor de infecção foi avaliado através de regressão logito ordenado. Foram ajustados modelos de riscos competitivos de Fine e Gray para avaliação da hiperglicemia como fator de risco de recidiva tumoral e modelos de regressão de Cox uni e multivariado para análise da sobrevida. Resultados: A incidência de hiperglicemia foi 43,6%. Os pacientes em puberdade apresentam chance 7,9 vezes maior de desenvolver hiperglicemia do que os pacientes impúberes (p=0,017). Para os indivíduos impúberes, o aumento de um ano na idade acarretou a redução de 14% na chance de ocorrência de hiperglicemia (p=0,039). A chance de hiperglicemia em pacientes com risco intermediário de recidiva foi 67% menor do que em pacientes com alto risco (p=0,020). No entanto, não se verificou diferença entre pacientes com risco baixo e alto de recidiva. No modelo de regressão logito ordenado, a hiperglicemia não representou fator de risco para a ocorrência de infecções durante o tratamento da LLA (p=0,840). Nos modelos de riscos competitivos de Fine e Gray, a hiperglicemia não se comportou como fator de risco para recidiva da LLA. Da mesma forma, nos modelos de regressão de Cox univariado e multivariado a hiperglicemia não se associou à ocorrência ou risco aumentado de óbito. Conclusões: Foram identificados como fator de risco para hiperglicemia durante o tratamento da LLA: idade (indivíduos impúberes mais jovens), puberdade em evolução ou completa e alto risco para recidiva da doença. A hiperglicemia não representou fator de risco para a ocorrência de infecções, recidiva da LLA ou óbito. Não foi observada diferença na incidência de hiperglicemia entre os indivíduos submetidos aos protocolos GBTLI-2009 e BFM 95 e 2002.
Objectives: To identify risk factors for the development of hyperglycemia during Acute Lymphocytic Leukemia (ALL) chemotherapy in pediatrics and to analyze its association with uneventful outcomes. To compare the incidence of hyperglycemia between patients treated according to different protocols, GBTLI-2009 and BFM 95 and 2002. Methods: Data were obtained from an anonymized database including a cohort of 188 pediatric patients diagnosed with ALL and treated at IOP/GRAACC/UNIFESP between 2004 and 2017. The effect of variables such as sex, age, ethnicity, family history of diabetes, puberty, nutritional status, ALL cell line, Philadelphia chromosome and Down syndrome on hyperglycemia development was analyzed by univariate and multivariate logistic regression models. The role of hyperglycemia as a risk factor for infection during ALL treatment was verified by ordinal logit regression. To analyze the effect of hyperglycemia on ALL incidence relapse and death, Fine and Gray competing risks models and univariate and multivariate Cox regression were adjusted, respectively. Results: The incidence of hyperglycemia was 43,6% in this cohort. Patients in puberty and post puberty were found to have 7,9-fold increased risk on developing hyperglycemia than pre-pubertal (p=0,017). Considering pre-pubertal patients, each subsequent year of age leaded to a 14% reduction on the chance to develop hyperglycemia (p=0,039). Patients with intermediate risk for ALL relapse had 67% less chance for hyperglycemia development than the ones with high risk of ALL relapse (p=0,020), although there were no differences between low-risk and high-risk individuals. Hyperglycemia was not found to be a risk factor for infection during ALL treatment on the ordinal logit regression model (p=0,840). Furthermore, it was not a significant risk factor for ALL relapse on Fine and Gray competing risks model, neither for death, on univariate and multivariate Cox regression. Conclusions: The identified risk factors for hyperglycemia during ALL chemotherapy were as follows: age (younger prepubertal individuals), puberty and intermediate risk for ALL relapse. Hyperglycemia did not lead to increased risk of infection, ALL relapse or death. There was no difference on hyperglycemia incidence between patients treated according GBTLI2009 or BFM 95 and 2002 protocols.
Objectives: To identify risk factors for the development of hyperglycemia during Acute Lymphocytic Leukemia (ALL) chemotherapy in pediatrics and to analyze its association with uneventful outcomes. To compare the incidence of hyperglycemia between patients treated according to different protocols, GBTLI-2009 and BFM 95 and 2002. Methods: Data were obtained from an anonymized database including a cohort of 188 pediatric patients diagnosed with ALL and treated at IOP/GRAACC/UNIFESP between 2004 and 2017. The effect of variables such as sex, age, ethnicity, family history of diabetes, puberty, nutritional status, ALL cell line, Philadelphia chromosome and Down syndrome on hyperglycemia development was analyzed by univariate and multivariate logistic regression models. The role of hyperglycemia as a risk factor for infection during ALL treatment was verified by ordinal logit regression. To analyze the effect of hyperglycemia on ALL incidence relapse and death, Fine and Gray competing risks models and univariate and multivariate Cox regression were adjusted, respectively. Results: The incidence of hyperglycemia was 43,6% in this cohort. Patients in puberty and post puberty were found to have 7,9-fold increased risk on developing hyperglycemia than pre-pubertal (p=0,017). Considering pre-pubertal patients, each subsequent year of age leaded to a 14% reduction on the chance to develop hyperglycemia (p=0,039). Patients with intermediate risk for ALL relapse had 67% less chance for hyperglycemia development than the ones with high risk of ALL relapse (p=0,020), although there were no differences between low-risk and high-risk individuals. Hyperglycemia was not found to be a risk factor for infection during ALL treatment on the ordinal logit regression model (p=0,840). Furthermore, it was not a significant risk factor for ALL relapse on Fine and Gray competing risks model, neither for death, on univariate and multivariate Cox regression. Conclusions: The identified risk factors for hyperglycemia during ALL chemotherapy were as follows: age (younger prepubertal individuals), puberty and intermediate risk for ALL relapse. Hyperglycemia did not lead to increased risk of infection, ALL relapse or death. There was no difference on hyperglycemia incidence between patients treated according GBTLI2009 or BFM 95 and 2002 protocols.