Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol.

Introduction: Acute myeloid leukaemia is the most common type of acute leukaemia in the world. Thus, the study of genetic alterations, such as single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve the prognosis and to increase the survival of these patients. However, there is no synthesis of evidence in the literature evaluating the quality of evidence and the risk of bias in the studies such that the results can be translated. Thus, this systematic review protocol aims to assess the impact of SNPs on genes involved in the metabolism of cytarabine and anthracyclines with respect to survival, treatment response and toxicity in patients with AML.
Methods: This systematic review protocol is based on PRISMA guidelines and includes searches in six electronic databases, contact with authors, repositories of clinical trials, and cancer research. Studies published in peer-reviewed journals will be included if they meet the eligibility criteria: (a) samples composed of individuals of any age, of both sexes, with a diagnosis of AML, regardless of the time of diagnosis of disease; (b) participants who have undergone or are undergoing cytarabine- and anthracycline-associated chemotherapy or cytarabine-only chemotherapy; and (c) in vivo studies. Studies that include patients with promyelocytic leukaemia (Fab type 3) will be excluded because this disease has different treatment. The process of study selection, data extraction, and evaluation/synthesis will be performed in duplicate. Assessment of methodological quality and risk of bias will be performed using the Cochrane Risk of Bias Tool for randomized clinical studies and the Downs-Black Checklist for cohort and case-control studies. The synthesis of evidence will include the level of evidence based on the GRADE protocol. A meta-analysis of the association between SNPs and outcomes may be performed based on Cochrane guidelines.
Discussion: It is expected that clinical decisions for AML patients will consider evidence-based practices to contribute to better patient management. In this way, we will be able to define how to treat patients with AML to improve their survival and quality of life.
Systematic Review Registration: PROSPERO CRD42018100750.