Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia.
TL;DR: This review presents the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants.
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Abstract: Despite major advances in the management and high cure rates of childhood acute lymphoblastic leukemia (ALL), patients still suffer from many drug-induced toxicities, sometimes necessitating dose reduction, or halting of cytotoxic drugs with a secondary risk of disease relapse. In addition, investigators have noted significant inter-individual variability in drug toxicities and disease outcomes, hence the role of pharmacogenetics (PGx) in elucidating genetic polymorphisms in candidate genes for the optimization of disease management. In this review, we present the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants. We then follow with a summary of the highest evidence drug-gene annotations with suggestions to move forward in implementing preemptive PGx for the individualization of treatment regimens for children with ALL.
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Neurotoxicity Associated with Treatment of Acute Lymphoblastic Leukemia Chemotherapy and Immunotherapy
TL;DR: An analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL is presented.
19
The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia
Tales Henrique Andrade da Mota,Ricardo Camargo,Estefânia Biojone,Ana Flávia Reis Guimarães,Fabio Pittella-Silva,Diêgo Madureira de Oliveira +5 more
TL;DR: In this article , the authors highlight the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment.
Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
Clara Vicente-Garcés,Elena Esperanza-Cebollada,Sara Montesdeoca,Montserrat Torrebadell,S. Rives,José Luis Dapena,Albert Català,Nuria Conde,Mireia Camós,Nerea Vega-García +9 more
TL;DR: This work validated a reliable and reproducible method to refine pediatric AL diagnosis, prognosis, and treatment, and demonstrated the feasibility of incorporating a targeted NGS panel into pediatric hematology practice.
8
A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia.
TL;DR: In this paper, the authors evaluated the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia.
3
Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs
Gabriela Burgueño-Rodríguez,Y. Méndez,N. Olano,Magdalena Schelotto,Luis Castillo,Ana María Soler,Julio da Luz +6 more
TL;DR: The importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia is shown, as mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry.
2
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