Myelodysplasia and Acute Myeloid Leukemia Following Therapy for Indolent Lymphoma with Fludarabine, Mitoxantrone, Dexamethasone (FND) Plus Rituximab and Interferon Alfa.

Treatment-related myelodysplasia (t-MDS) can occur following chemotherapy, especially with DNA-damaging agents such as alkylators or topoisomerase II inhibitors. Antimetabolites such as the nucleoside analogs have only infrequently been associated with post therapy MDS (t-MDS). In a prospective chemo-immunotherapy trial between 1997–2003 in patients with stage IV indolent lymphoma, 202 patients were treated and 8 have developed MDS between 2–5 years after therapy, including 4 who received only fludarabine, mitoxantrone, and dexamethasone (FND) for 6–8 courses, with or without rituximab. The other 4 MDS patients received other agents including alkylators, either as salvage chemotherapy or as part of the initial regimen. Complex cytogentic abnormalities were present in all patients. Abnormalities of chromosome 7 were present in six of the eight, three of whom received FND ± rituximab therapy only. The abnormalities of chromosome 7 were monosomy 7 in four (one of which had add 7p in the remaining chromosome), one del 7q, and one der 7. MDS with features classically associated with DNA damaging agents can occur following therapy with the FND combination, with or without rituximab.