Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone

Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylli ne 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexa methasone was added to the regimen for the partial responders and the nonre sponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 week s. Amifostine was administered intravenously 3 times a week at 3 dose level s (200 mg/M-2, 300 mg/M2, and 400 mg/M-2) to cohorts of 10 patients each. T herapy has been continued for 1 year in responders. Twenty-nine have comple ted at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blast s (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secon dary MDS, No differences were noted in response rates among the 3 dose leve ls. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%), Three had a triple lineage response, 10 had a double line age response, and 9 had a single lineage response (8 of 9 in absolute neutr ophil count [ANC] and 1 had more than a 50% reduction in packed red blood c ell transfusions). Fifteen patients responded only after the addition of de xamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in bloo d transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to a ppear, and continued improvement in counts was seen up to 12 months of ther apy and beyond. This study supports the feasibility of treating patients wi th MDS with the unique approach of cytoprotection and anticytokine therapie s as well as the principle that prolonged commitment to treatment is desira ble when noncytotoxic agents are administered. (C) 2000 by The American Soc iety of Hematology.