Abstract
Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) is a distinct biologic subtype of AML that represents 25–34% of all AML diagnoses and associates with especially inferior outcomes compared to non-MRC AML. Typically, patients with AML-MRC experience low remission rates following intensive chemotherapy and a median overall survival of merely 9–12 months. In light of these discouraging outcomes, it has become evident that more effective therapies are needed for patients with AML-MRC. Liposomal daunorubicin–cytarabine (CPX-351) was approved in 2017 for adults with newly diagnosed AML-MRC and those with therapy-related AML (t-AML), and remains the only therapy specifically approved for this patient population. Other studies have also demonstrated the efficacy of the hypomethylating agent (HMA) azacitidine as upfront therapy for AML-MRC patients, which, to date, is the most common treatment employed for patients unable to tolerate the more intensive CPX-351. HMAs and venetoclax combinations have also been evaluated, but additional studies utilizing these agents in this specific subgroup are needed before conclusions regarding their role in the therapeutic armamentarium of AML-MRC patients can be reached. Currently, many studies are ongoing in attempts to further improve outcomes in this historically ill-fated patient group.
Highlights
Acute myeloid leukemia (AML) is a disease of the myeloid lineage of blood cells that results in a block in differentiation of myeloid cells and uninhibited growth of leukemic blasts that constrain the growth of normal blood cells [1] Clinical sequelae often include malaise and fatigue, infections, bleeding and/or bruising, and possibly bone pain [1]
A compelling study by Chen and colleagues proposes that myelodysplastic syndrome (MDS) does not directly evolve into AML, but rather parallel clonal evolutionary changes occur in which pre-MDS stem cells and/or MDS stem cells concurrently develop into two separate cell populations: an MDS population and a separate population of pre-AML/AML-stem cells [18]
Had the same complete response (CR) + CRi rate as de novo AML patients (67%), and had a longer median duration of CR + CRi (NR; 12.5 months to not reached (NR)) and median overall survival (OS) (NR; 14.6 months to NR) when compared to de novo AML patients. This combination still warrants investigation in patients previously treated with hypomethylating agent (HMA), as they were excluded in this trial, as well as in the other subsets of AML with myelodysplasia-related changes (AML-MRC) besides secondary AML
Summary
Acute myeloid leukemia (AML) is a disease of the myeloid lineage of blood cells that results in a block in differentiation of myeloid cells and uninhibited growth of leukemic blasts that constrain the growth of normal blood cells [1] Clinical sequelae often include malaise and fatigue, infections, bleeding and/or bruising, and possibly bone pain [1]. The disease is classified into multiple biologic subtypes according to genetic abnormalities, including both cytogenetic and molecular changes, degree of differentiation, myeloid lineage involved, and dysplastic changes [3]. These classifications associate with disease prognosis and predict outcomes for patients [3]. The aim of this review article is to discuss the leukemic transformation of MDS and disease behavior of AML-MRC, to discuss the challenges associated with treating patients with AML-MRC, to summarize data from clinical trials that have informed therapeutic approaches for this AML subtype, and to discuss potential future directions
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