In acquired AA, following an insult (likely viral), there is immune-mediated damage to stem cells, resulting in an inflammatory immune response. There is oligoclonal expansion of cytotoxic CD8 T cells, but the more important component comprises the CD4 T cells, with expansion of Th1 (clonal) and Th17 cells and reduced and dysfunctional Tregs. Two approaches to drug treatment are (1) IST with ATG and ciclosporin and (2) eltrombopag, resulting in direct stem cell stimulation. The different possible responses to treatment are scenario 1, where there are too few HSCs to respond to either IST or eltrombopag (the role of combination therapies is being explored). In scenario 2, there is almost a complete peripheral blood recovery, but biopsy usually shows a hypocellular BM, and often patients have macrocytosis. Scenario 3 shows complete recovery of blood and BM. In scenario 4, there is recovery with emergence of clones (such as −7 or other myeloid-specific mutations), which have a growth advantage, eventually resulting in features of hypocellular MDS. PNH, paroxysmal nocturnal hemoglobinuria.