Abstract
IntroductionAcute 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.MethodsThis 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.DiscussionIt 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 registrationPROSPERO CRD42018100750
Highlights
Acute myeloid leukaemia is the most common type of acute leukaemia in the world
The study of genetic alterations related to the appearance of Acute myeloid leukaemia (AML), such as somatic mutations and single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve prognosis [3, 11,12,13] and to increase the survival of these patients [2, 5]
Population Studies will be accepted (a) when the sample is composed of individuals of any age, of both sexes, with a diagnosis of acute myeloid leukaemia, and independent of the time of diagnosis of the disease; (b) when participants who have undergone or are undergoing cytarabine- and anthracycline-associated [11, 14] or isolated cytarabine chemotherapy—the latter being the main and earliest chemotherapy used for AML [29, 37]; and (c) when they are in vivo
Summary
Acute myeloid leukaemia is the most common type of acute leukaemia in the world. 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. Acute myeloid leukaemia (AML) is a malignant and heterogeneous [1] haematopoietic disease [2] characterized by an abnormal growth of proliferative, clonal and highly differentiated white blood cells [3, 4] These cells infiltrate the bone marrow and stimulate the production of progenitor or abnormal white cells, preventing the system from maturing its cells to perform adequate defence functions in the organism [5], and infiltrate other tissues, which can lead to relapse and an increased risk of death [6]. The study of genetic alterations related to the appearance of AML, such as somatic mutations and single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve prognosis [3, 11,12,13] and to increase the survival of these patients [2, 5]
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