Izzie serves Alex a "Dear John" letter and leaves town when she's under the impression that he got her fired. She pops up a few episodes later in the sixth season, hoping to make things work between them when she finds out that it wasn't him. While Alex is happy that she's cancer-free, he realises that he deserves better. It's really too bad, since the pair of them were almost as iconic as Derek and Meredith. Alex truly cared for her, but in the end, things turned out for the better and he got the closure that he deserved.
Watch it here.