Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5–10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers. There is less data on the incidence of second malignancies after reduced-intensity conditioning, but it may not be lower. The types of solid tumors reported in excess include melanoma and other skin cancers; cancers of the oral cavity and head and neck, brain, liver, uterine cervix, thyroid, breast, lung; and possibly gastrointestinal cancers. Therapy-related myeloid neoplasms (t-MN) are more common after autologous SCT and may be related mostly to pre-transplant therapies. Post-transplant lymphoproliferative disease is donor-cell-derived lymphoma that is more common after allogeneic SCT with T-cell depletion or intensive immune-suppression state. Second malignancies are most often treated similarly to the standard therapy for similar malignancies. Lifelong cancer screening and prevention interventions are required for all transplantation survivors.
