Maamari Dimitri, El-Khoury Habib, Saifi Omran, Muwakkit Samar A, Zgheib Nathalie K
Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Pharmgenomics Pers Med. 2020 Aug 12;13:295-317. doi: 10.2147/PGPM.S239602. eCollection 2020.
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.
尽管儿童急性淋巴细胞白血病（ALL）的治疗取得了重大进展且治愈率很高，但患者仍遭受许多药物诱导的毒性反应，有时需要减少剂量，或停止使用细胞毒性药物，从而带来疾病复发的二次风险。此外，研究人员注意到药物毒性和疾病转归存在显著的个体间差异，因此药物遗传学（PGx）在阐明候选基因中的遗传多态性以优化疾病管理方面发挥着作用。在本综述中，我们除了介绍疗效外，还展示了与ALL患儿治疗中出现的主要毒性相关的PGx数据，重点关注最可能的种系PGx变异。然后，我们总结了证据最充分的药物 - 基因注释，并提出了推进对ALL患儿治疗方案进行个体化的前瞻性PGx实施的建议。
