The purpose of this review is to update knowledge on therapy-related myeloid
neoplasms (t-MNs), taken into account the new 2008 WHO classification, new
genome-wide approaches for the definition of susceptibility towards t-MN and the
introduction of new more aggressive treatments in cancer patients.
t-MNs are an increasing matter in cancer survivors treated with chemoradiotherapy. One
of the major concerns in hematologic malignancies is childhood acute lymphoblastic
leukemia (ALL), in which the leukemogenic role of extended etoposide/teniposide
treatment, concomitant intensive antimetabolite and asparaginase, granulocyte colonystimulating
factor (G-CSF) and prophylactic cranial radiotherapy use have been
established. In high-risk Hodgkin lymphoma, 3% t-MNs have been observed at 10-year
follow-up with the escalated BEACOPP schedule, versus 0.4% with ABVD. In
lymphoproliferative diseases the new drugs fludarabine and lenalidomide may increase
the risk of second tumors, when associated to other cytotoxic therapies. Among solid
tumors, breast cancer is most frequently associated to t-MN. The risk is correlated to
higher chemotherapy doses, radiotherapy, use of G-CSF, but also independent from
treatment, suggesting a genetic predisposition to both diseases. Radiotherapy plays a
role also in female pelvic tumors and in testicular cancer, when associated to cisplatin.
The risk of t-MN is not negligible, although below 2% in most series. This is particularly
significant for younger cancer patients and during the first 5 years after the primary
malignancies. Efforts should be maximized to identify susceptibility factors to identify
patients at risk, in whom more leukemogenic drugs and schedules should be avoided.