Treatment-related myelodysplasia following fludarabine combination chemotherapy

Although myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) are rare following fludarabine monotherapy, the risk of these diseases may potentially be increased when fludarabine is combined with cyclophosphamide or mitoxantrone due to synergistic effects on the inhibition of DNA repair. Among 137 patients treated with fludarabine combination regimens, ten patients developed MDS/sAML, including one who had received no other therapy. Six patients had abnormalities of chromosomes 5 and/or 7. The crude rate of MDS/sAML was 2.5% for previously untreated patients, and 9.3% for pretreated patients (p=0.28). The rate of MDS/sAML following fludarabine combination therapy is higher than that previously reported for fludarabine monotherapy.