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

Abstract

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.

Keywords: Acute myeloid leukemia with myelodysplasia-related changes; CPX-351; Chemotherapy; Cytogenetic analysis; Diagnosis; Morphologic evaluation; Mutational analysis; Targeted agents.

Image 1

Morphologic features of multilineage dysplasia. A, Dysplastic changes are usually most prominent on the bone marrow aspirate or peripheral blood smear. In this case, erythroid precursors show irregular nuclear contours (white arrow), granulocytes demonstrate clumped nuclear chromatin without complete segmentation and hypogranular cytoplasm (black arrows), and a small, hypolobated megakaryocyte is present (white arrowhead). Some blast cells are small (black arrowheads) and may be mistaken for lymphocytes (Wright-Giemsa, ×600). B, The bone marrow biopsy specimen is hypercellular with a heterogenous cellular composition. Dysplastic small and large megakaryocytes, with detached nuclear lobes, are easily identified on the biopsy specimen (some marked with arrows) (H&E, ×400).

Figure 1

Simplified diagnostic algorithm for AML-MRC.^, AML, acute myeloid leukemia; AML-MRC, acute myeloid leukemia with myelodysplasia-related changes; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm.