Pharmacologic Therapies to Prevent Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML.

Acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation: a retrospective study from a single institution

“… 22 The role of other targeting agents and combination therapies with donor lymphocyte infusion are currently under investigation and may contribute to maintenance therapy options after allo-HSCT. 23 However, more evidence is required to establish effective strategies to prevent AML relapse after allo-HSCT.…”

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

“…Furthermore, the lack of comorbidity is an issue in identifying risk factors for NRM. Third, there is a recent trend in using MRD status in pre- and post-allo-SCT setting to classify MRD-positive patients who would benefit from HMAs maintenance after allo-SCT ( 41 ). However, MRD assessment data was scarce in published included trials precluding a subgroup analysis.…”

The Elephant in The Room: AML Relapse Post Allogeneic Hematopoietic Cell Transplantation

“…Preemptive and maintenance strategies post allo-HCT to prevent the relapse to occur is also imperative (70). Enhancing the GVL effect using HMAs is a promising approach, as well as the use of maintenance tyrosine kinase inhibitors such as FLT3 inhibitors post allo-HCT (71)(72)(73)(74)(75)(76). Moreover, progress in accurate quantification and monitoring of measurable residual disease post allo-HCT is helpful in predicting impending morphologic relapse that prompts treatment initiation (77,78).…”