STANDARD AND LOW-DOSE CHEMOTHERAPY FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES

The myelodysplastic syndromes (MDS) are a heterogeneous group of disor ders with an invariably fatal outcome. Other than bone marrow transpla ntation, no treatment has been able to alter the natural history of MD S. As a result, there has been an interest in identifying new and more effective chemotherapeutic agents. Many of the drugs that have been e valuated in an attempt to increase remissions and prolong survival wer e selected because of their activity in acute myeloid leukemia. Thus c ytarabine has been the most widely studied drug. Although numerous stu dies suggested activity for low-dose cytarabine (LoDAC), a careful ana lysis of the data identified a complete remission (CR) rate of less th an 20%, without meaningful clinical benefit. The issue of LoDAC was fi nally put to rest by a randomized trial in which survival was no bette r than with supportive care. 5-Azacytidine induces cellular differenti ation by hypomethylation of DNA. Phase II trials noted CRs in fewer th an 10% of patients, with response rates under 30%, although additional patients appeared to experience hematologic and clinical benefit. A r andomized trial of 5-azacytidine versus supportive care failed to demo nstrate a survival benefit. One of the most promising new agents is th e topoisomerase inhibitor topotecan, which achieves CRs in more than 3 0% of patients. Combinations of this drug with other active agents are in development. Obviously, new treatment strategies are needed to imp rove the outcome of MDS patients. Combination approaches incorporating new, active agents should have sound scientific rationale, targeting biological differences among the various MDS subtypes. (C) 1998 Elsevi er Science Ltd. All rights reserved.