Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials

Seongseok Yun, Nicole D. Vincelette, Ivo Abraham, Keith D Robertson, Martin E Fernandez-Zapico, Mrinal M Patnaik

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

Background: Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population. Methods: Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS. Results: Overall survival (OS) rate was 33.2 vs. 21.4 % (RR 0.83, 95 % CI 0.71–0.98) and overall response rate (ORR) 23.7 vs. 13.4 % (RR 0.87, 95 % CI 0.81–0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 % CI 0.64–0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact. Conclusion: Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.

Original languageEnglish (US)
Article number68
JournalClinical Epigenetics
Volume8
Issue number1
DOIs
StatePublished - Jun 14 2016

Fingerprint

decitabine
Azacitidine
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Epigenomics
Stem Cell Transplantation
DNA Methylation
Cytogenetics
Survival Rate
Randomized Controlled Trials
Bone Marrow
Survival
DNA
Therapeutics
Population
Neoplasms

Keywords

  • AML
  • DNA hypomethylating agents
  • Epigenetics
  • MDS

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Developmental Biology
  • Genetics(clinical)

Cite this

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title = "Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials",
abstract = "Background: Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population. Methods: Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS. Results: Overall survival (OS) rate was 33.2 vs. 21.4 {\%} (RR 0.83, 95 {\%} CI 0.71–0.98) and overall response rate (ORR) 23.7 vs. 13.4 {\%} (RR 0.87, 95 {\%} CI 0.81–0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 {\%} CI 0.64–0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact. Conclusion: Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.",
keywords = "AML, DNA hypomethylating agents, Epigenetics, MDS",
author = "Seongseok Yun and Vincelette, {Nicole D.} and Ivo Abraham and Robertson, {Keith D} and Fernandez-Zapico, {Martin E} and Patnaik, {Mrinal M}",
year = "2016",
month = "6",
day = "14",
doi = "10.1186/s13148-016-0233-2",
language = "English (US)",
volume = "8",
journal = "Clinical Epigenetics",
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T1 - Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome

T2 - a systematic review of hypomethylating agents trials

AU - Yun, Seongseok

AU - Vincelette, Nicole D.

AU - Abraham, Ivo

AU - Robertson, Keith D

AU - Fernandez-Zapico, Martin E

AU - Patnaik, Mrinal M

PY - 2016/6/14

Y1 - 2016/6/14

N2 - Background: Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population. Methods: Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS. Results: Overall survival (OS) rate was 33.2 vs. 21.4 % (RR 0.83, 95 % CI 0.71–0.98) and overall response rate (ORR) 23.7 vs. 13.4 % (RR 0.87, 95 % CI 0.81–0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 % CI 0.64–0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact. Conclusion: Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.

AB - Background: Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population. Methods: Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS. Results: Overall survival (OS) rate was 33.2 vs. 21.4 % (RR 0.83, 95 % CI 0.71–0.98) and overall response rate (ORR) 23.7 vs. 13.4 % (RR 0.87, 95 % CI 0.81–0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 % CI 0.64–0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact. Conclusion: Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.

KW - AML

KW - DNA hypomethylating agents

KW - Epigenetics

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