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

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 predetermined eligibility criteria. Randomeffects 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.

A Retrospective Observation of Treatment Outcomes Using Decitabine-Combined Standard Conditioning Regimens Before Transplantation in Patients With Relapsed or Refractory Acute Myeloid Leukemia

“…DAC is confirmed to be well-tolerated in patients with relapsed or refractory AML, even in the cases with increased age and comorbid burden ( 26 , 27 ). Considering that the maximum tolerated dose of DAC can reach up to 1,500–2,500 mg/m 2 and no clear correlation between dosage and response has been found ( 13 ), a high-dose schedule (75 mg/m 2 × 1 and 50 mg/m 2 × 1) and a low-dose schedule (25 mg/m 2 /day × 3) of DAC, as part of standard conditioning regimens, were compared in allo-HSCT patients with relapsed or refractory AML in this study.…”

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

“…Several drugs targeting aberrant DNA methylation, such as 5-aza-2′-deoxycytidine (5-aza-dC), have already been utilized for the therapy of refractory or relapsed cancer patients [ 12 , 13 ]. 5-aza-dC exerts anticancer activity by effectively reducing DNA methylation levels and restoring the expression of P16 [ 14 , 15 ].…”

Synergistic inhibitory effect of Smo inhibitor jervine and its combination with decitabine can target Hedgehog signaling pathway to inhibit myelodysplastic syndrome cell line

“…Decitabine is used with chemotherapy or molecular therapy. However the efficacy of its combinational use is much variable [29]. Decitabine in combination with chidamide, showing synergistic cytotoxicity in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [30].…”