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Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia

Authors Maamari D, El-Khoury H, Saifi O, Muwakkit SA, Zgheib NK

Received 29 April 2020

Accepted for publication 20 July 2020

Published 12 August 2020 Volume 2020:13 Pages 295—317

DOI https://doi.org/10.2147/PGPM.S239602

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Martin H Bluth


Dimitri Maamari1 ,* Habib El-Khoury1 ,* Omran Saifi,1 Samar A Muwakkit,2 Nathalie K Zgheib3

1Faculty of Medicine, American University of Beirut, Beirut, Lebanon; 2Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3Department of Pharmacology and Toxicology, American University of Beirut, Faculty of Medicine, Beirut, Lebanon

*These authors contributed equally to this work

Correspondence: Samar A Muwakkit; Nathalie K Zgheib Email sm03@aub.edu.lb; nk16@aub.edu.lb

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.

Keywords: pharmacogenetics, childhood ALL, implementation

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