Hypomethylating agent-based post-transplant strategies to maximize the outcome of high-risk acute myeloid leukemia after allogeneic stem cell transplantation

Expert Rev Hematol. 2020 Sep;13(9):959-969. doi: 10.1080/17474086.2020.1804355. Epub 2020 Aug 14.

Abstract

Introduction: Clinical outcomes of patients diagnosed with high-risk acute myeloid leukemia (AML) are poor, and relapse or refractoriness is main cause of treatment failure, even in those who underwent standard allogeneic stem cell transplantation (allo-SCT). Therefore, innovative or additional approaches are necessary to overcome refractoriness to the graft-versus-leukemia (GVL) effect immediately after allo-SCT.

Areas covered: Hypomethylating agents (HMA) present a feasible option that can be adopted during the post-transplant phase. Moreover, combination strategies based on HMA may induce a synergistic effect by promoting anti-leukemic effects that overcome residual leukemic burden, and it is a well-tolerated therapeutic option for high-risk disease. Relevant literatures published in the last 30 years were searched from PubMed to review the topic of AML, allo-SCT, and HMAs.

Expert opinion: Post-transplant therapy is strongly needed to improve the outcomes of allogeneic transplantation for certain AML patients classified with high-risk disease. In that sense, prophylactic and preemptive HMAs are a promising additive therapy for allogeneic recipients.

Keywords: High-risk; acute myeloid leukemia; allogeneic stem cell transplantation; hypomethylating agent; minimal residual disease.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / pharmacology
  • Azacitidine / therapeutic use
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • DNA Methylation / drug effects*
  • Decitabine / pharmacology
  • Decitabine / therapeutic use
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Mutation
  • Postoperative Care*
  • Transplantation, Homologous
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Decitabine
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Azacitidine