Therapy-related myeloid neoplasms

The purpose of this review is to update knowledge on therapy-related myeloid neoplasms (t-MN), taking 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-MN are an increasing matter in cancer survivors treated with chemoradiotherapy. One of the major concerns in hematologic malignancies is childhood acute lymphoblastic leukemia, in which the leukemogenic role of extended etoposide/teniposide treatment, concomitant intensive antimetabolite and asparaginase, granulocyte colony-stimulating factor (G-CSF) and prophylactic cranial radiotherapy use have been established. In high-risk Hodgkin lymphoma, 3% t-MN have been observed at 10-year follow-up with the escalated bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone (BEACOPP) schedule, versus 0.4% with doxorubicin/bleomycin/vinblastine/dacarbazine (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.