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

Abstract and Introduction


Objectives: Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) represents a high-risk and somewhat diverse subtype of AML, and substantial confusion exists about the pathologic evaluation needed for diagnosis, which can include the patient's clinical history, cytogenetic analysis, mutational analysis, and/or morphologic evaluation. Treatment decisions based on incomplete or untimely pathology reports may result in the suboptimal treatment of patients with AML-MRC.

Methods: Using a PubMed search, diagnosis of and treatment options for AML-MRC were investigated.

Results: This article reviews the current diagnostic criteria for AML-MRC, provides guidance on assessments necessary for an AML-MRC diagnosis, summarizes clinical and prognostic features of AML-MRC, and discusses potential therapies for patients with AML-MRC. In addition to conventional chemotherapy, treatment options include CPX-351, a liposomal encapsulation of daunorubicin/cytarabine approved for treatment of adults with AML-MRC; targeted agents for patients with certain mutations/disease characteristics; and lower-intensity therapies for less fit patients.

Conclusions: Given the evolving and complex treatment landscape and the high-risk nature of the AML-MRC population, a clear understanding of the pathology information necessary for AML-MRC diagnosis has become increasingly important to help guide treatment decisions and thereby improve patient outcomes.


The classification of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) in general includes patients with acute myeloid leukemia (AML) that develops after myelodysplastic syndromes (MDSs) or MDS/myeloproliferative neoplasms (MPNs), AML with multilineage dysplasia, and de novo AML with certain MDS-related cytogenetic abnormalities.[1] The classification of AML-MRC overlaps somewhat with the traditional term "secondary AML," which includes patients with AML that develops from an antecedent hematologic disorder (including MDS and MDS/MPN), as well as those with therapy-related AML that develops after prior cytotoxic therapy, radiotherapy, or immunosuppressive therapy;[2] however, therapy-related AML is not included in the AML-MRC category.

It has been estimated that AML-MRC represents up to 48% of all adult AML cases.[3,4] Outcomes for patients with AML-MRC, or more generally those with secondary AML, following conventional combination chemotherapy, are poor compared with many other AML subtypes, with lower remission rates and shorter overall survival (OS).[2,5–8] Several new agents have been approved over the past few years for the treatment of various AML subgroups, driving an evolving and complex treatment landscape. Given the high-risk nature of AML-MRC, a clear understanding of the AML-MRC diagnosis and appropriate treatment options is important to help improve outcomes.