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

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

Article highlights

• High-risk acute myeloid leukemia is a very difficult disease to treat because it often displays resistance to chemotherapeutic agents or a graft-versus-leukemia (GVL) effect with aggressive induction treatment followed by standard allogeneic stem cell transplantation (allo-SCT).

• Innovative or additional approaches are needed to overcome refractoriness to the GVL effect immediately after allogeneic transplantation.

• Hypomethylating agents (HMAs) seem to beneficially influence the GVL effect by increasing the immunological visibility of leukemia cells and modulating the activity of NK and T cells without increasing the incidence of graft-versus-host disease.

• Combination strategies based on HMAs may induce synergistic anti-leukemic effects to overcome the residual leukemic burden, and they are a well-tolerated therapeutic option for allogeneic recipients with high-risk AML.

• It is critical to identify patients who can benefit from HMAs after allo-SCT based on their genetic mutational profiles and minimal residual disease (MRD) analyses.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.