Therapy-related myeloid neoplasms: pathobiology and clinical characteristics.

摘要: Therapy-related myeloid neoplasms (t-MNs) are serious long-term consequences of cytotoxic treatments for an antecedent disorder. t-MNs observed after ionizing radiation as well conventional chemotherapy including alkylating agents, topoisomerase-II-inhibitors and antimetabolites. In addition, adjuvant use recombinant human granulocyte-colony stimulating factor may also increase the risk t-MNs. There is clinical biological overlap between high-risk de novo myelodysplastic syndromes acute leukaemia suggesting similar mechanisms leukaemogenesis. Human studies animal models point to a prominent role genetic susceptibilty in pathogenesis Common variants have been identified that modulate t-MN risk, some cancer predisposition syndromes. either case, establishing leukaemic phenotype requires acquisition somatic mutations – most likely induced by treatment. Knowledge specific nature initiating exposure has allowed identification crucial pathogenetic these be modelled vitro vivo. Prognosis patients with dismal at present, only curative approach majority individuals haematopoietic stem cell transplantation, which characterized high transplant-related mortality rates. Novel transplantation strategies using reduced intensity conditioning regimens novel drugs demethylating agents targeted therapies await testing improve outcome. Ultimately, individual assessment factors translate into tailored establish strategy reducing incidences without jeopardizing therapeutic success rates primary disorders.