Diagnosis and Treatment of Patients With AML-MRC

Abstract and Introduction

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.

Introduction

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.

Table 1. 2016 World Health Organization Criteria for AML-MRC ¹
Patients with ≥20% blasts in peripheral blood or bone marrow who meet any of the following criteria^a:
Clinical history	A history of MDS or MDS/MPN, such as CMML and aCML
Morphologic features	Multilineage dysplasia in ≥50% of ≥2 cell lineages (ie, dysgranulopoiesis, dyserythropoiesis, or dysmegakaryopoiesis) in the absence of NPM1 or biallelic CEBPA mutations
Cytogenetic abnormalities	An MDS-related cytogenetic abnormality, as indicated below
	Complex karyotype: ≥3 unrelated abnormalities, not including the recurrent cytogenetic abnormalities encountered in AML	Unbalanced abnormalities: −7/del(7q) del(5q)/t(5q) i(17q)/t(17p) −13/del(13q) del(11q) del(12p)/t(12p) idic(X)(q13)	Balanced abnormalities: t(11;16)(q23.3;p13.3) t(3;21)(q26.2;q22.1) t(1;3)(p36.3;q21.2) t(2;11)(p21;q23.3) t(5;12)(q32;p13.2) t(5;7)(q32;q11.2) t(5;17)(q32;p13.2) t(5;10)(q32;q21.2) t(3;5)(q25.3;q35.1)

aCML, atypical chronic myeloid leukemia, BCR-ABL1 negative; AML, acute myeloid leukemia; AML-MRC, acute myeloid leukemia with myelodysplasia-related changes; CMML, chronic myelomonocytic leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm.
^aExcludes patients with therapy-related AML (ie, arising after cytotoxic chemotherapy, radiotherapy, or immunotherapy) or a cytogenetic abnormality qualifying for a diagnosis of AML with recurrent genetic abnormalities.