Donor-derived malignancy after allogeneic stem cell transplantation: a rare but well recognized complication

Relapse after allogeneic stem cell transplantation (allo-SCT) remains a major drawback of the procedure, occurring in approximately 30-60% of patients. While most relapses arise from the original malignant clone, they may also emerge from donor-derived cells harbouring genetic defects that confer a malignant phenotype. Although initially considered an exceedingly rare phenomenon, advances in molecular techniques for chimerism analysis have led to an increase in case reporting and awareness of donor-derived malignancy (DDM), with a rising estimated incidence. Differentiating between relapse of the original disease and DDM is critical, as they are associated with distinct treatment approaches and outcomes. In the case of DDM, there may also be significant ethical implications for the donor, with the dilemma of whether donors should be notified and whether high-risk donor populations - such as older individuals and those providing umbilical cord blood grafts - should be screened for germline mutations or clones of indeterminate potential prior to donation. Since the first report of a DDM case in 1971, 64 cases were reported through 2009. The aim of this study was to systematically review the literature and critically analyze the DDM cases reported from 2009 to 2024, identifying potential common characteristics that may predispose to DDM development.