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

Clinical and Prognostic Features of AML-MRC

AML-MRC represents up to 48% of all adult AML cases.[3,4] It occurs primarily in elderly patients (median age, 68 years) and is uncommon in children.[3,4,14,15] AML-MRC occurs more often as de novo AML with MDS-related cytogenetic changes or multilineage dysplasia than as AML arising secondarily from prior documented MDS or MDS/MPN.[4,12] By definition, patients with AML-MRC have a high frequency of adverse cytogenetics, including complex karyotype, and they often present with severe pancytopenia.[3,4,7,14,15] AML-MRC is also characterized by a relatively high frequency of ASXL1 mutations (35% of patients) and low frequencies of FLT3 and DNMT3A mutations.[14] A recent study that evaluated mutation frequencies also found that patients with de novo AML-MRC tended to have a higher frequency of TP53 mutations, and those with antecedent MDS or MDS/MPN had a higher frequency of SETBP1, RUNX1, and SRSF2 mutations compared with the other evaluated groups; meanwhile, patients with AML-MRC tended to have lower frequency of SF3B1 mutations than patients with MDS and NPM1, FLT3-ITD, and NRAS mutations than patients with AML other than AML-MRC.[28] Characteristics of 262 patients with AML-MRC underscored the challenging nature of this group: 57% were 75 years or older, 53% had poor-risk cytogenetics, and approximately one-third were reported to have had antecedent MDS.[29]

In general, patients with AML-MRC have a worse prognosis, with lower remission rates and shorter OS, compared with patients who have most other AML subtypes. In a cohort of 100 patients with AML, those with AML-MRC had significantly shorter median OS and progression-free survival, as well as a lower complete remission (CR) rate, than those with AML-NOS. AML-MRC was identified as a predictor of poor OS independent of age or cytogenetic risk.[17] Similarly, in a cohort of 85 patients with AML, those with AML-MRC had a significantly lower CR rate (48% vs 78%) than those with other AML subtypes, although the 2-year OS rates were similar for the two groups.[14] Results from a larger-scale retrospective analysis of a cohort of 449 patients with AML indicated that those with AML-MRC had significantly shorter median OS (10 vs 16 months) and disease-free survival (5 vs 12 months), as well as a lower CR rate (61% vs 78%), compared with patients with AML-NOS.[7]

Different multivariate analyses have reported conflicting results regarding factors associated with a poorer prognosis among patients with AML-MRC. Results from one study identified older age (≥60 years), adverse cytogenetics, and antecedent MDS or MDS/MPN as independent factors associated with shorter OS and disease-free survival in patients with AML-MRC.[7] A separate study also identified antecedent MDS or MDS/MPN and de novo AML with MDS-related cytogenetics as conferring a worse prognosis compared with patients with AML-MRC who had a diagnosis based on multilineage dysplasia (median OS of 5.3 and 6.3 vs 20.4 months).[8] In contrast, results from a second analysis indicated that MDS-related cytogenetics, antecedent MDS, and multilineage dysplasia did not influence OS in patients with AML-MRC. Of note, this analysis did identify ASXL1 and TP53 mutations as independent factors associated with shorter OS.[15] Another study found that patients with AML-MRC who had RUNX1 mutations had shorter OS compared with those who had any AML with RUNX1 mutations or AML-NOS with wild-type RUNX1 (11 vs 19 months and not reached, respectively), suggesting AML-MRC with a RUNX1 mutation represents a poor prognosis group.[30]