Use of decitabine for patients with refractory or relapsed acute myeloid leukemia: a systematic review and meta-analysis

Hematology. 2019 Dec;24(1):507-515. doi: 10.1080/16078454.2019.1632407.

Abstract

Background: Approximately, one-third of adult patients with acute myeloid leukemia (AML) are refractory to initial induction chemotherapy and relapse occurs in most patients who achieve remission. This study evaluates the efficacy of decitabine in the management of refractory or relapsed AML. Methods: After literature search in electronic databases (Google Scholar, Embase, Ovid, and PubMed) studies were selected by following pre-determined eligibility criteria. Random-effects meta-analyses were performed to achieve effect sizes of complete remission (CR) rate, response rate (RR), and median survival after therapy. Subgroup analyses were performed with regards to use of decitabine with either epigenetics-based therapy, molecular therapy or chemotherapy. Results: Twenty studies were included (310 patients; age 55.1 years [95% confidence interval (CI): 43.8, 66.4]; 57% [52%, 63%] males). Overall RR was 46.1% [95% CI: 36.1%, 56.1%]. Overall CR rate was 23.5% [95% CI: 22.1%, 24.9%] but was 14.85% [95% CI: 3.8%, 25.9%] for decitabine with epigenetics-based therapies, 15.4% [95% CI: 6.7%, 24.0%] for decitabine with immunotherapy or molecular therapy, 34.8% [95% CI: 18.7%, 50.9%] for decitabine with chemotherapy, and 37.5% [36.4%, 38.7%] for decitabine with chemotherapy and molecular therapy. Median survival was 7.2 months [95% CI: 5.17, 9.3]. Major adverse events were neutropenia, nausea/vomiting, infections, fatigue, febrile neutropenia, diarrhea, thrombocytopenia, anemia, anorexia, leukopenia, hemorrhage, and hyperglycemia. Conclusion: Decitabine in combination with chemotherapy or molecular therapy has shown efficacious properties in refractory or relapsed AML patients.

Keywords: 5-aza-2′-deoxycytidine; Decitabine; acute myeloid leukemia; chemotherapy; meta-analysis; molecular therapy; remission; survival.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • DNA (Cytosine-5-)-Methyltransferase 1 / antagonists & inhibitors
  • DNA Methylation / drug effects*
  • Decitabine / administration & dosage
  • Decitabine / adverse effects
  • Decitabine / pharmacology
  • Decitabine / therapeutic use*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Fatigue / chemically induced
  • Febrile Neutropenia / chemically induced
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gene Expression Regulation, Leukemic / drug effects*
  • Hematologic Diseases / chemically induced
  • Humans
  • Hyperglycemia / chemically induced
  • Immunotherapy
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Recurrence
  • Remission Induction
  • Salvage Therapy*

Substances

  • Antimetabolites, Antineoplastic
  • Enzyme Inhibitors
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human