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Secondary leukemia in the setting of allogeneic HSCT refers to leukemia of donor cell origin or a new leukemia developing in surviving patient cells. Both are extremely rare complications, raising important questions on leukemogenesis. Recently, the Seattle team has suggested that transfer with the donor graft of otherwise silent malignant cells could also be responsible for leukemias arising from donor cells. However, no clear evidence links these secondary leukemias to cGVHD. Nevertheless, with increasing use of older donors (especially for patients receiving reduced intensity conditioning) special attention must be given to the search for hematological abnormalities in the donor and of clear need for donor’s surveillance.

The development of new leukemias in patient cells is most likely related to cytotoxic conditioning therapy; there is no evidence to support a role of cGVHD.