Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia

The prognosis of acute myeloid leukemia (AML) is influenced by both disease-intrinsic and patient-related factors. In particular, AML following myelodysplastic syndrome (MDS) (AML with myelodysplasia-related changes, AML-MRC) has a poor prognosis. We hypothesized that patients with cytopenias prior to AML, but no known prior MDS, may share biologic features with AML-MRC. We evaluated 140 AML patients without prior MDS who had complete blood count (CBC) data available 6-36 months prior to their diagnosis. Cytopenia, defined as clinically unexplained thrombocytopenia or macrocytic anemia, was present in 29/140 (21%) patients. Compared to non-cytopenic patients, AML patients with prior cytopenia were older and more often met morphologic or cytogenetic criteria for AML-MRC. Prior cytopenia was associated with shorter survival in patients with intermediate-risk cytogenetics (median OS 4.2 versus 24.1 months, p<0.0001), but not in patients with adverse-risk cytogenetics (median OS 4.4 versus 6.0 months, p=0.57). Prior thrombocytopenia, but not macrocytic anemia, was significantly associated with shorter overall survival (p=0.01) independent of treatment approach, karyotype risk, and age on multivariable analysis. Our data suggest that AML patients with prior cytopenias have features similar to AML-MRC, and in particular support the use of prior unexplained thrombocytopenia as an independent marker of high-risk disease.