Atg And Cyclosporine

While ISTs, such as antithymocyte globulin (ATG) and cyclosporine, have remarkably altered the clinical course of patients with AA, these drugs have been of limited benefit in MDS patients. While patients with AA can be cured with IST, the response to IST in MDS patients is neither curative nor sustained beyond a year in most cases.33 In one study, 16 of 42 patients with RA, RARS, or RAEB who were treated with 4 days of ATG became transfusion independent. The highest response rate was seen in RA patients (61%), whereas none of the patients with RARS responded.34 Most responding patients had hypocellular marrows, and responses to ATG in both MDS and AA patients seems to be associated with expression of the HLA DR15,35 even though patients with other HLA types also respond. Predictive models can help determine which factors in MDS patients are more likely to predict for response to ATG therapy, such as having RA, normal cytogenetics, pancytopenia, or a hypocellular bone marrow. Cyclosporine alone has also produced responses in MDS patients.3637


Amifostine, an organic thiophosphate with antioxi-dant activity, was evaluated in the mid to late 1990s in MDS patients. Hematologic improvements were seen in 84% (5/18 patients) in the first amifostine trial,38 but this response rate could not be confirmed in subsequent small phase II studies.39-41 In general, responses were brief, and some responses were lost by the time the subsequent cycle of amifostine was due to be administered. Combinations of amifostine with other agents have also shown only modest activity.42

Arsenic trioxide, an FDA-approved treatment for acute promyelocytic leukemia, has also shown modest activity in MDS patients. Hematologic improvements were seen in two small early clinical trials,4344 and several patients had major erythroid responses with loss of transfusion dependence. Myelosuppression and other toxicities were generally mild to moderate and manageable, included grade 3 and 4 myelosuppres-sion. In a study of arsenic trioxide and thalidomide, trilineage hematologic responses were seen in 2/28 patients, both of whom carried the inv(3)(q21q26.2) cytogenetic abnormality.45 As our knowledge grows, the use of therapies without widespread efficacy in specific subsets of MDS patients (such as those with inv(3)(q21), if these results are confirmed by others) may be useful.

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