Diagnosis and Treatment of Patients With Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC)

Daniel A. Arber, MD; Harry P. Erba, MD, PhD


Am J Clin Pathol. 2020;154(6):731-741. 

In This Article


AML-MRC accounts for a substantial proportion of AML cases and includes patients with antecedent hematologic malignancies (eg, MDS) as well as those with de novo AML who have multilineage dysplasia and/or MDS-related cytogenetic abnormalities. AML-MRC primarily occurs in elderly patients and is associated with an increased probability of adverse cytogenetics and worse clinical outcomes. Therefore, there is a need for rapid karyotype analysis or, if not possible, the use of FISH panels to quickly identify the majority of patients with AML-MRC who do not have a history of MDS or multilineage dysplasia. The extra expense of such testing should be balanced with the treatment benefit afforded to the patient by making a diagnosis quickly. NPM1 and CEBPA, along with FLT3, should be evaluated by RT-PCR, as these results typically are obtained more quickly than next-generation sequencing panels, and the results are important for the diagnosis of AML-MRC and for informing treatment decisions.

If therapy is pursued with curative intent in patients with AML-MRC, then allogeneic HCT should be considered in the first-line treatment plan. The use of regimens capable of inducing remission in this population is critical, since patients are typically not considered eligible for allogeneic HCT unless in complete remission. Furthermore, these remissions ideally should be durable and deep, as well as not lead to excessive toxicity so as not to preclude subsequent allogeneic HCT. Recently approved chemotherapeutic regimens have been shown to induce such remissions in this patient population. Therefore, the identification of patients with AML-MRC at the time of initial diagnosis is critical to the optimal treatment of these patients.

CPX-351 was the first agent to demonstrate improved outcomes, including a higher HCT rate compared with conventional chemotherapy (7 + 3 regimen) in patients with AML-MRC, and it is currently the only agent specifically approved for this high-risk population. It is not yet understood how this regimen may compare with less-intensive strategies, such as venetoclax in combination with HMAs, or more intensive regimens such as FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin). The combination of CPX-351 chemotherapy with targeted agents has also not yet been evaluated. Given the suboptimal outcomes for patients with AML-MRC, clinicians may choose to combine targeted agents with active chemotherapy regimens, such as CPX-351, instead of waiting for safety and efficacy data from combination studies. Therefore, clinical studies of these combinations are needed urgently; until such data are available, clinicians should exercise great caution when combining agents, as they may have overlapping toxicities, particularly myelosuppression. The goal of therapy (ie, curative approach vs palliative treatment) may help to inform regimen selection until randomized trial data are available in specific subpopulations of patients, including AML-MRC.

Genomics, epigenetics, and proteomics may ultimately identify more precise definitional markers in AML and eliminate the need for the current category of AML-MRC. As understanding of the biologic drivers of AML improves, it is expected that therapy selection may transition to targeting relevant biologic drivers of different AML subgroups.