Introduction: Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients.Materials and Methods: The Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome.Results: The meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III–IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone.Conclusions: The current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies.

Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1–76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7–145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9–70.2%) and 40.2% (95% CI, 28.0–53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1–64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3–32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4–53.9%). Approximately 29% of the patients suffered from grades 2–4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1–19.8%) and 21.1% (95% CI, 18.8–23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.