The maturation block evident in patients with MDS has provided a rationale for more than a decade of treatments with "differentiation-inducing" agents. However, none of the clinical trials with such agents have provided clear evidence of a differentiating effect, despite the demonstration of in vitro differentiation effects on leukemia cell lines. The agents studied include retinoids, vitamin D3 analogs, cytarabine (at one time thought to induce differentiation at low doses), phenylbutyrate, and hexamethylene bisac-etamide. Overall, the results have been generally disappointing.46 Low-dose cytarabine continues to be used for some MDS patients, perhaps based on a randomized study comparing low-dose cytarabine to supportive care, in which a 35% hematologic response was seen. However, in that study cytarabine did not improve survival or delay progression to acute myelo-cytic leukemia (AML).47 czs-Retinoic acid was also shown to be no better than supportive care in another randomized trial.48 A more recent trial reported hema-tologic improvement in 11/19 patients with the newer vitamin D3 analog, calcitriol.49
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