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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1580-1587
Patients with myelodysplastic syndromes benefit from palliative
therapy with amifostine, pentoxifylline, and ciprofloxacin with or
without dexamethasone
Azra Raza,
Huma Qawi,
Laurie Lisak,
Tanja Andric,
Saleem Dar,
Colleen Andrews,
Paramesuaran Venugopal,
Sefer Gezer,
Stephanie Gregory,
Jerome Loew,
Erwin Robin,
Shelby Rifkin,
Wei-Tong Hsu, and
Ray-Win Huang
From the Rush Cancer Institute and the Departments of Pathology and
Biostatistics, Rush-Presbyterian-St. Luke's Medical Center, Chicago;
Ingall's Memorial Hospital, Harvey; and Northwest Community Hospital,
Arlington Heights, IL.
Thirty-five patients with myelodysplastic syndrome (MDS) were
registered on protocol MDS 96-02 and were receiving continuous therapy
with pentoxifylline 800 mg 3 times a day and
ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to
the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M2, 300 mg/M2, and 400 mg/M2) to cohorts of 10 patients each. Therapy has been
continued for 1 year in responders. Twenty-nine have completed 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
blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five
had secondary MDS. No differences were noted in response rates among
the 3 dose levels. 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 lineage response, and 9 had a single lineage
response (8 of 9 in absolute neutrophil count [ANC] and 1 had more
than a 50% reduction in packed red blood cell transfusions). Fifteen
patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved
ANC, 11 of 22 demonstrated more than 50% reduction in blood
transfusions, improved Hb levels, or both, and 7 of 22 showed
improvement in platelet counts. Interestingly, the responses were
frequently slow to appear, and continued improvement in counts was seen
up to 12 months of therapy and beyond. This study supports the
feasibility of treating patients with MDS with the unique approach of
cytoprotection and anticytokine therapies as well as the principle that
prolonged commitment to treatment is desirable when noncytotoxic agents
are administered.
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