When it comes to acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), a disorder characterized by multilineage dysplasia, myelodysplastic syndrome (MDS)-related karyotype, or history of prior MDS, treatment may need to be more nuanced. A study published in the American Journal of Hematology has found that not all diagnostic criteria for AML-MRC define high-risk patients; there may be specific subgroups who benefit from different therapeutic interventions.

Researchers enrolled 415 patients with AML-MRC who had a median age of 70 years and were treated between 2013 and 2018 in order to assess clinical outcomes based on the diagnostic criteria of AML-MRC, therapy type, and mutation profile.

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Secondary-type (ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) mutations were found in 37 of 95 evaluable patients (93%); mutations in ASXL1, BCOR, SF3B1, SRSF2, and U2AF1 tended to appear in dominant clones. In multivariate analysis, AML-MRC subtype, age, and serum lactate dehydrogenase levels were found to be independent predictors of outcome.

Patients with AML-MRC diagnosed solely on the basis of dysplasia (AML-MRC-M) were found to experience better overall survival compared with patients with other AML-MRC subtypes (hazard ratio [HR], 0.56; 95% CI, 0.38-0.84; P =0.004). Intensive therapy was associated with improved overall survival in patients with AML-MRC-M (HR, 0.42; 95% CI 0.19-0.94; P =0.036) and with improved event-free survival in patients with AML-MRC-M or AML-MRC diagnosed on the basis of prior diagnosis of MDS or MDS/myeloproliferative neoplasms without prior treatment  (AML-MRC-H; HR, 0.26; 95% CI, 0.10-0.63; P =0.003).

When compared with a group of 468 patients with AML of varying risk who did not meet the criteria for AML-MRC, patients with AML-MRC-M or AML-MRC-H had similar outcomes as patients with intermediate-risk AML.

“[T]he overall adverse prognosis in AML-MRC is driven by the presence of MDS-defining cytogenetic abnormalities,” the researchers concluded. They suggested that patients may benefit from being stratified by complex karyotype, whether they were treated for a secondary leukemia, and whether they have specific somatic or secondary-type mutations.

Reference

  1. Montalban‐Bravo G, Kanagal‐Shamanna R, Class CA, et al. Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy [published online February 28, 2020]. Am J Hematol. doi: 10.1002/ajh.25769