Diagnosis and classification

Pathophysiology

Epidemiology and prognosis

Treatment

Summary

References

INTRODUCTION

Acute myeloid leukemia (AML) is a heterogenous, aggressive myeloid malignancy. In 2018, an estimated 19,520 new cases and 10,670 deaths occurred in the United States. Although strides have been made in AML treatment using novel therapies and small molecule inhibitors, the 5-year overall survival (OS) is only approximately 27%. Contributing to this dismal prognosis is the increasing rates of secondary AML (sAML), which describe a subset of AML that arises from either an antecedent hematologic disorder (AHD) such as myelodysplastic syndrome (MDS), or are related to prior exposure to cytotoxic chemotherapy agents or radiation therapy. The incidence of sAML ranges from 10% to 35% of AML cases. This article focuses on the epidemiology, diagnosis, pathogenesis, molecular, and treatment of sAML.

DIAGNOSIS AND CLASSIFICATION

Secondary AML occurs by 2 separate mechanisms, either through an antecedent hematologic disorder (AHD) or prior chemotherapy or radiation therapy, and the classification of AML has begun to reflect this etiology. In a study evaluating the ontogeny of AML, distinct somatic mutations differentiated AML subtypes between de novo AML, AML-AHD (labeled as s-AML), and therapy-related AML (t-AML). Multiple analyses have been studied to determine the transformational cause for the change from AHD to AML. Clonal evolution in AML is common, with many of the mutations occurring as random events, then acquiring a cooperating mutation leading to proliferation of the malignant clone. In 2008, the World Health Organization (WHO) introduced the diagnosis of AML with myelodysplasia-related changes (AML-MRC), which was later expanded to specific criteria in the 2016 WHO classification system. This newer classification requires a prior history of MDS, MDS-associated cytogenetic abnormalities, or multilineage dysplasia, but specifically excludes prior cytotoxic chemotherapy or radiation therapy and entity-defining recurring cytogenetic abnormalities. The classification of AML-MRC has a high frequency of mutations in ASXL1 mutations, and a low rating of NPM1, FLT3, and DNMT3A mutations. Patients with AMLMRC who have either the ASXL1 mutation or TP53 mutations are associated with shorter OS. In a retrospective study of Chinese patients with AML-MRC, patients had significantly shortened complete response (CR) rates, disease-free survival (DFS), and OS compared with AML-NOS patients.