What is the prognosis of acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC)?

Updated: Aug 03, 2020
  • Author: Angie Duong, MD; Chief Editor: Aliyah R Sohani, MD  more...
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Answer

Patients with acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) generally have a poor prognosis. [18]  The percentage of patients who achieve complete remission is lower with this form of AML than with other AML types. [19]  As mentioned previously, cases arising in association with an myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN) may show slower progression and thus may be less clinically aggressive. The prognosis is also affected by associated cytogenetic abnormalities: high-risk cytogenetic abnormalities include -5, -7, del(5q), abn(3q), and complex karyotype. [20]

The presence of MYC oncoprotein expression appears to be an independent poor prognostic factor in patients with AML-MRC. [21]  AML-MRC subtype, patient age, and serum lactate dehydrogenase levels also appear to be independent predictors of outcome, with better overall survival in patients with AML-MRC with multilineage dysplasia and AML-MRC with history of prior MDS or MDS/myeloproliferative neoplasm (MDS/MPN), whereas worse outcomes are associated with AML-MRC with cytogenetic abnomalities or AML-MRC with a history of previously treated MDS or MDS/MPN. [22]

The clinical and prognostic significance of AML‐MRC as defined by morphologic criteria alone has been debated. [23]  In a study of de novo AML lacking MDS-related cytogenetic abnormalities, patients who fulfilled criteria for AML-MRC based solely on morphologic criteria did not show significantly different event-free survival compared to patients with AML not otherwise specified (AML-NOS) who lacked multilineage dysplasia. [24]  The same study also ananlyzed individual dysplastic features and found the presence of more than 50% micromegakaryocytes and/or over 50% hypogranulated myeloid cells to be associated with adverse event‐free survival, suggesting that a more restrictive definition of morphologic dysplasia may have greater relevance in terms of risk stratification in patients lacking cytogenetic abnormalities. [24]  Overall, the finding of multilineage dysplasia still appears to confer an adverse prognosis, albeit not as poor as that in cases with high-risk cytogenetic abnormalities. [2]

Finally, the increased use of myeloid-related gene mutation panels has identified mutations of potential adverse prognostic signfiicance in AML-MRC, including TP53  and ASXL1. [25]  AML patients with normal karyotypes who have isolated NPM1 mutation without accompanying FLT3 mutations, or those with biallelic CEBPA mutations are considered to have favorable prognosis. [2, 23]  The lack of adverse prognostic significance of multilineage dysplasia in AML with mutated NPM1 or biallelic CEBPA mutations [1, 8, 9]  supports the guidance of the revised 4th edition of the World Health Organization (WHO) classification of not including these entities within the spectrum of AML-MRC, even if morphologic dysplasia is present. [2]


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