Use of low-dose decitabine with or without tyrosine kinase inhibitors in advanced phase chronic myelogenous leukemia: a systemic review and metaanalysis

Abstract

RationaleProgression of Chronic Myelogenous Leukemia (CML) to more advanced phases can involve hypermethylation, which is correlated to resistance or intolerance to imatinib. This hypermethylation has also been found to be a negative prognostic factor independent of imatinib response and from CML phase, thus decitabine, a hypomethylating agent, can be an attractive treatment option for advanced phase CML.ObjectiveThis systemic review and meta-analysis aims to investigate the role of low-dose decitabine among patients with advanced phase CML.MethodologyThis was performed according to the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)ResultsFour (4) studies from 86 articles screened were eligible to be assessed in this systemic review and meta-analysis. These were phase I/II trials involving 81 advanced phase CML patients and used low-dose decitabine (5 to 20 mg/m2), with two studies using tyrosine kinase inhibitors. Outcomes of hematologic and cytogenetic response, and survival were assessed in the meta-analysis; with hematologic response being favored among advanced phase CML patients upon exposure with low-dose decitabine (p=0.05). Survival was also favored among responders to low-dose decitabine, however this was not significant.Discussion and ConclusionLow-dose decitabine can be an effective and safe treatment option in advanced phase CML, especially in more frail patients that could not tolerate more intensive chemotherapy regimens. However, this study is limited by few studies available on this topic, thus further randomized controlled trials can be investigated to define the role of decitabine and its optimal dose among this subset of patients.