The need for rapid cytogenetics in the era of vyxeos therapy for acute myeloid leukemia with myelodysplasia related changes (AML-MRC)

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Conference Proceeding

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Modern Pathology


Background: AML-MRC criteria includes i) history of Myelodysplastic syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN) or ii) MDS- related cytogenetic abnormality or iii) Multilineage dysplasia (>50 % dysplasia in at least 2 lineages). Recently, the drug Vyxeos was approved for the treatment of adults with newly diagnosed therapy related AML or AML-MRC and confers a significantly better survival than standard therapy. We aimed to identify the proportion of cases diagnosed as AML-MRC solely based on MDS associated cytogenetic abnormality (i.e. not meeting the morphologic criteria and/or not having history of MDS or MDS/MPN). Design: A cohort of 64 AML-MRC cases were re-examined morphologically to assess for and exactly quantify the degree of dysplasia. We examined bone marrow aspirate smears, touch preps, bone marrow biopsy and clot sections to assess for dysplasia. We categorized dysplasia into three categories; less than 10%, 10-50% and >50%. The other categories were normal/no dysplasia and not enough nonblast cells to accurately assess for dysplasia. Results: Out of 64 cases of AML- MRC, 53 had complex cytogenetics (83%), 5 had del (5q) or t (5q) (8%), 4 cases had -7 or del (7q) (6%) and 2 had other MDS associated abnormalities (3%). Only 30% of cases had more than 50% dysplasia in two or more lineages. 70% of cases required either a relevant clinical history (MDS or MDS/MPN) or MDS associated cytogenetic abnormalities for AML-MRC diagnosis. More than 50% dysplasia in two lineages was seen in 34% of cases with complex cytogenetics, 20% of del (5q)/ t(5q) cases and 0% of -7/ del (7q) cases. Most frequently reported dysplastic cell line was myeloid (45%) followed by megakaryocytic (38%) followed by erythroid (16%). 22% of cases had cytogenetic abnormalities other than those tested on a routine MDS or AML FISH panel. Conclusions: 63% of our cases needed an MDS associated cytogenetic abnormality to render a diagnosis of AML-MRC. 22% of cases had cytogenetic abnormalities which would have been missed on a routine MDS or AML FISH panel. In the absence of an AML-MRC diagnosis, patients are put on the standard 7+3 chemotherapy regimen and cannot be generally switched to Vyxeos at a later time. Considering the routine turnaround time of 7-21 days for conventional chromosomal analysis, it is imperative to have a preliminary cytogenetic result (generally 5 cell based) or a rapid chromosomal microarray analysis within 2-3 days of AML diagnosis to enable Vyxeos therapy.





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