Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia

Abstract

Background/objective The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. Design We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. Subjects/methods Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. Conclusions These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

As consequências da sobrevida de pacientes pediátricos portadores de leucemia

“…Sintomas compatíveis com transtorno de déficit de atenção e déficits no processamento mental, velocidade, memória de trabalho e desempenho resolutivo se combinam para deixar sobreviventes intelectualmente e academicamente desfavorecidos(TURHAN et al, 2018). De acordo com o trabalho de EGSET et al, 2021, estudos de sobreviventes de longo prazo sugerem que efeitos neurocognitivos tardios podem persistir até a idade desenvolvimento do tecido adiposo dessas crianças na idade adulta são atualmente desconhecidas(VISENTIN et al, 2019). Ademais, BROWNE et al, 2022, relaciona a leucemia linfoblástica aguda com o desenvolvimento de quadros de obesidade.Pressupõe-se, ainda, que o mecanismo de obesidade nesses pacientes seja multifatorial, o que pode abranger outras alterações hormonais, interferência medicamentosa, especialmente pelo uso de corticoides, redução da prática de exercícios físicos e anormalidades do balanço energético(ALVES et al, 2009).…”