Is Traditional Low-Dose Chemotherapy (Cytarabine/Melphalan) Still an Option for the Treatment of Myelodysplastic Syndromes?

In the United Kingdom, low-dose cytarabine (Ara-C) is now considered the standard of care for nonintensive therapy of myelodysplastic syndromes (MDS) with > 10% blasts and acute myeloid leukemia (AML). It remains an inexpensive and effective therapy in older patients with AML or MDS who are not fit for intensive chemotherapy. Low-dose Ara-C is ineffective for adverse-risk karyotype, and the early death rate is high (9%). The incidence of grade 3/4 infection and hemorrhage is as high as 17% and 9%, respectively. A more favorable outcome is linked to the administration of ≥ 4 courses and to the achievement of complete remission (CR). The largest published series showed an overall response rate of 44% in 180 patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation and a progression-free survival time of 9 months. Low-dose melphalan cannot be routinely recommended but should be considered in a subgroup of elderly patients with MDS with > 10% blasts or AML, normal karyotype, and hypocellular bone marrow, where durable CR rates of 30% are reported with minimal side effects. Preliminary phase III trial data suggest that demethylating agents produce superior overall survival compared with other low-dose options.