Two-step clustering and classification model for decision making in BMF. In the first step of the model, K-means clustering grouped cases into clusters A and B, which correlated with clinical diagnosis. Cluster A was enriched for cases of FA and DC, patients who had AA at young ages, and cases with AA and single or bilineage cytopenias over a broad spectrum of age but most frequently 20 and 50 years old. In contrast, cluster B was enriched for classical inherited BMF, including early disease onset DBA and SDS, and cases of FA and DC in middle age. In the second step, a classification model specific to cluster A was developed for binary prediction of cases as acquired and inherited. The cluster A–specific algorithm accurately predicted the BMF etiology in 79% of cases with IBMFS (model sensitivity) and 92% of cases with likely immune BMF (specificity) when TL data were available. The model lost accuracy without TL, a top predictive factor. However, in the absence of TL data, IBMFSs were rarely seen in adults with SAA and no family history or a phenotype suggestive of inherited disease; presence of PNH clone >1% within this group had a specificity of 100% for acquired AA. yo, years old.