Francesco Felicetti1,2, Alessia Sofia Cento3, Paolo Fornengo4, Maurizio Cassader2, Raffaella Mastrocola3, Fabrizio D'Ascenzo2,5, Fabio Settanni6, Andrea Benso2,6, Emanuela Arvat2,7, Massimo Collino8, Franca Fagioli9,10, Manuela Aragno3, Enrico Brignardello1. 1. Transition Unit for Childhood Cancer Survivors, Città della Salute e della Scienza Hospital, Turin, Italy. 2. Department of Medical Science, University of Turin, Turin, Italy. 3. General Pathology Unit, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. 4. Department of Medicine, Città della Salute e della Scienza Hospital, Turin, Italy. 5. Division of Cardiology, Città della Salute e della Scienza Hospital, Turin, Italy. 6. Division of Endocrinology, Diabetology and Metabolism, Città della Salute e della Scienza Hospital, Turin, Italy. 7. Division of Oncological Endocrinology, Città della Salute e della Scienza Hospital, Turin, Italy. 8. Department of Drug Science and Technology, University of Turin, Turin, Italy. 9. Division of Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy, Città della Salute e della Scienza Hospital, Turin, Italy. 10. Department of Public Health and Paediatric Sciences, University of Turin, Turin, Italy.
Abstract
BACKGROUND: Among survivors of pediatric acute lymphoblastic leukemia (ALL), those who received hematopoietic stem cell transplantation (HSCT) conditioned with total-body irradiation (TBI) show the highest risk of late complications, including cardiovascular (CV) disease. Advanced glycation end products (AGEs) have been associated with CV disease in diabetes mellitus and other clinical conditions. This study explores AGEs plasma levels, inflammatory status, and lipid profile in survivors of pediatric ALL who received HSCT conditioned with TBI. PROCEDURE: Inclusion criteria were (a) previous diagnosis of ALL at age < 18 years, treated with HSCT conditioned with TBI; (b) age > 18 at the time of the study enrollment; (c) off-therapy for at least five years. Radiotherapy other than TBI, preexisting heart disease, glucose metabolism impairment, body mass index > 25, active graft versus host disease (GvHD), smoking, or treatment with cholesterol lowering medications were exclusion criteria. Eighteen survivors and 30 age-matched healthy controls were enrolled. RESULTS: AGEs plasma levels were markedly higher in ALL survivors than in healthy subjects (2.15 ± 2.21 vs 0.29 ± 0.15 pg/mL, P < 0.01). Survivors also showed higher levels of high-sensitivity C-reactive protein (2.32 ± 1.70 vs 0.88 ± 1.09 mg/dL, P < 0.05), IL-1β (7.04 ± 1.52 vs 4.64 ± 2.02 pg/mL, P < 0.001), IL17 (37.44 ± 3.51 vs 25.19 ± 6.34 pg/mL, P < 0.001), an increased glutathione/reduced glutathione ratio (0.085 ± 0.07 vs 0.041 ± 0.036, P < 0.05) and slight alterations in their lipid profile. CONCLUSIONS: Our data show AGEs accumulation and chronic inflammation in ALL survivors who received HSCT conditioned with TBI. These alterations may contribute to the increased risk of CV disease reported in these subjects.
BACKGROUND: Among survivors of pediatric acute lymphoblastic leukemia (ALL), those who received hematopoietic stem cell transplantation (HSCT) conditioned with total-body irradiation (TBI) show the highest risk of late complications, including cardiovascular (CV) disease. Advanced glycation end products (AGEs) have been associated with CV disease in diabetes mellitus and other clinical conditions. This study explores AGEs plasma levels, inflammatory status, and lipid profile in survivors of pediatric ALL who received HSCT conditioned with TBI. PROCEDURE: Inclusion criteria were (a) previous diagnosis of ALL at age < 18 years, treated with HSCT conditioned with TBI; (b) age > 18 at the time of the study enrollment; (c) off-therapy for at least five years. Radiotherapy other than TBI, preexisting heart disease, glucose metabolism impairment, body mass index > 25, active graft versus host disease (GvHD), smoking, or treatment with cholesterol lowering medications were exclusion criteria. Eighteen survivors and 30 age-matched healthy controls were enrolled. RESULTS: AGEs plasma levels were markedly higher in ALL survivors than in healthy subjects (2.15 ± 2.21 vs 0.29 ± 0.15 pg/mL, P < 0.01). Survivors also showed higher levels of high-sensitivity C-reactive protein (2.32 ± 1.70 vs 0.88 ± 1.09 mg/dL, P < 0.05), IL-1β (7.04 ± 1.52 vs 4.64 ± 2.02 pg/mL, P < 0.001), IL17 (37.44 ± 3.51 vs 25.19 ± 6.34 pg/mL, P < 0.001), an increased glutathione/reduced glutathione ratio (0.085 ± 0.07 vs 0.041 ± 0.036, P < 0.05) and slight alterations in their lipid profile. CONCLUSIONS: Our data show AGEs accumulation and chronic inflammation in ALL survivors who received HSCT conditioned with TBI. These alterations may contribute to the increased risk of CV disease reported in these subjects.
Authors: Alberto Romano; Ester Del Vescovo; Serena Rivetti; Silvia Triarico; Giorgio Attinà; Stefano Mastrangelo; Palma Maurizi; Antonio Ruggiero Journal: J Pers Med Date: 2022-05-27
Authors: Francesca Rossi; Chiara Tortora; Martina Di Martino; Alessandra Di Paola; Daniela Di Pinto; Maria Maddalena Marrapodi; Maura Argenziano; Elvira Pota Journal: PLoS One Date: 2022-07-21 Impact factor: 3.752