Influence of cytarabine metabolic pathway polymorphisms in acute myeloid leukemia induction treatment

• Published in: Leukemia & lymphoma Vol. 58; no. 12; pp. 2880 - 2894
• Main Authors: Megías-Vericat, Juan Eduardo, Montesinos, Pau, Herrero, María José, Moscardó, Federico, Bosó, Virginia, Martínez-Cuadrón, David, Rojas, Luis, Rodríguez-Veiga, Rebeca, Boluda, Blanca, Sendra, Luis, Cervera, José, Poveda, José Luis, Sanz, Miguel Ángel, Aliño, Salvador F.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.12.2017
• Subjects: acute myeloid leukemia; Adolescent; Adult; Aged; Alleles; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacokinetics; CDA; Cytarabine; Cytarabine - administration & dosage; Cytarabine - pharmacokinetics; DCK; efficacy; Female; Genotype; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - mortality; Male; Metabolic Networks and Pathways; Middle Aged; Pharmacogenomic Variants; polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Remission Induction; Retrospective Studies; Young Adult; CDA; polymorphism; Cytarabine; acute myeloid leukemia; DCK; efficacy
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2017.1323267

Cytarabine is considered the most effective chemotherapeutic option in acute myeloid leukemia (AML). The impact of 10 polymorphisms in cytarabine metabolic pathway genes were evaluated in 225 adult de novo AML patients. Variant alleles of DCK rs2306744 and CDA rs602950 showed higher complete remission (p = .024, p = .045), with lower survival rates for variant alleles of CDA rs2072671 (p = .015, p = .045, p = .032), rs3215400 (p = .033) and wild-type genotype of rs602950 (p = .039, .014). Induction death (p = .033) and lower survival rates (p = .021, p = .047) were correlated to RRM1 rs9937 variant allele. In addition, variant alleles of CDA rs532545 and rs602950 were related to skin toxicity (p = .031, p = .049) and mucositis to DCK rs2306744 minor allele (p = .046). Other toxicities associated to variant alleles were hepatotoxicity to NT5C2 rs11598702 (p = .032), lung toxicity (p = .031) and thrombocytopenia to DCK rs4694362 (p = .046). This study supports the interest of cytarabine pathway polymorphisms regarding efficacy and toxicity of AML therapy in a coherent integrated manner.