ABSTRACT The long-term outcome of acute lymphoblastic leukemia has improved dramatically due to the development of more effective treatment strategies. L-asparaginase (ASNase) is one of the main drugs used and causes death of leukemic cells by systematically depleting the non-essential amino acid asparagine. Three main types of ASNase have been used so far: native ASNase derived from Escherichia coli, an enzyme isolated from Erwinia chrysanthemi and a pegylated form of the native E. coli ASNase, the ASNase PEG. Hypersensitivity reactions are the main complication related to this drug. Although clinical allergies may be important, a major concern is that antibodies produced in response to ASNase may cause rapid inactivation of ASNase, leading to a worse prognosis. This reaction is commonly referred to as "silent hypersensitivity" or "silent inactivation". We are able to analyze hypersensitivity and inactivation processes by the measurement of the ASNase activity. The ability to individualize the ASNase therapy in patients, adjusting the dose or switching patients with silent inactivation to an alternate ASNase preparation may help improve outcomes in those patients. This review article aims to describe the pathophysiology of the inactivation process, how to diagnose it and finally how to manage it.

RESUMO Objetivo: Avaliar o impacto da terapia sobre a densidade mineral óssea (DMO) e composição corporal em sobreviventes da leucemia linfoide aguda (LLA), tratados de acordo com os protocolos brasileiros do Grupo Cooperativo Brasileiro de Tratamento de Leucemia Linfoide Aguda na Infância (GBTLI), LLA-93 e LLA-99. Métodos: Em estudo transversal com 101 pacientes, avaliaram-se a composição corporal e a DMO por meio da densitometria óssea, interpretando-a conforme a faixa etária e a população de referência. Foi considerado grupo de risco para baixa DMO valores de z-escore entre -1,1 e -1,9 no grupo dos menores de 20 anos. Compararam-se os valores da DMO com características clínicas, tratamento recebido e composição corporal. Foram utilizados os testes qui-quadrado, exato de Fisher, razão de verossimilhança e t de Student, com nível de significância de 5%. Resultados: Foram encontradas 2% de fraturas, 2% de osteonecrose e 2,9% de baixa DMO. No grupo de pacientes com menos de 20 anos, três apresentaram baixa DMO. Os 16 pacientes com risco para baixa DMO exibiram menores valores em vértebras lombares L1-L4 (p=0,01), corpo total (p=0,005) e valores mais baixos de massa magra (p=0,03). No grupo de 22 pacientes com mais de 20 anos, dez demonstraram osteopenia. Conclusões: O baixo impacto do tratamento sobre a DMO neste estudo ratifica o conceito de que o ganho de massa óssea ocorre com o aumento da idade e que o tratamento não influencia tal processo. A população de risco para baixa DMO demonstrou valores menores de massa óssea, podendo beneficiar-se de um acompanhamento em longo prazo para uma possível toxicidade óssea.

ABSTRACT Objective: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. Methods: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher’s exact test, likelihood ratio and Student’s t-test were applied, with a 5% significance level. Results: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. Conclusions: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.