Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha

Treatment-related myelodysplasia (t-MDS) occurs less frequently with the nucleoside analogs than with DNA-damaging agents such as alkylators or topoisomerase II inhibitors. In a chemoimmunotherapy trial conducted between 1997 and 2003 in patients with stage IV indolent lymphoma, 202 patients were treated and 8 have developed MDS between 1 and 5 years after therapy, including 4 who received only fludarabine, mitoxantrone, and dexamethasone (FND) for 6 to 8 courses, with or without rituximab, followed by interferon alpha (IFN-α). Complex cytogenetic abnormalities were present in all patients. Abnormalities of chromosome 7 were present in 6 of the 8 patients, 3 of whom received only FND ± rituximab and IFN-α. The abnormalities of chromosome 7 were monosomy 7 in 4 patients (1 of which had add 7p in the remaining chromosome); 1 del 7q; and 1 der 7. MDS with features classically associated with DMA-damaging agents can occur following therapy with FND, with or without rituximab, and IFN-α.