Association of amifostine and erythropoietin for the treatment of anemia in myelodysplastic syndromes

Pellegrino Musto, Alberto Grossi, Francesca Balestri, Potito R. Scalzulli, Giovanni D'Arena, Maria G. Sanpaolo, Saverio F. Mantuano

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Abstract

Amifostine add recombinanl erythropoietin (r-EPO) have been demonstrated to be effective, as single drugs, in improving anemia in a limited proportion of patients affected by myelodysplastic syndromes (MDS). In order to verify a possible synergistic effect of these two drugs, which have different mechanisms of action, we performed a pilot study using a combination of amifostine and r-EPO in 9 patients with transfusion-dependent MDS (5 males and 4 females, mean age 62 years, range 48-79). Four patients had refractory anemia (RA), 3 RA with excess of blasts (RAEB), 2 RAEB in transformation (RAEB-T or AML, according to FAB or WHO classifications, respectively). Mean Hb level was 7.1 g/dl (range 6.2-7.9), with a mean requirement of 4 transfusions/month (range 1-7). Amifostine (Ethyol, Schering-Plough) was administered t.i.w. as 15′ i.V. infusion of 200 mg/sqm, for 46 weeks. r-EPO (Eprex, Janssen-Cilag; Globuren, Dompe'-Biotec; Neo-Recormon, Roche) was given subcutaneously at the fixed dose of 10.000 U/d (3 patients) or on alternate day (6 patients). Two patients achieved a complete erythroid response (abolition of transfusional support) and 3 additional patients experienced a partial erythroid response, with > 50% reduction of their supportive therapy. WBC count significantly increased in 2 patients, while one patient obtained a stable increase in PLT count (from 15 to 55 × IOE9/1). No trilineage response was observed. Interestingly, 3 erythroid responses (2 partial and 1 complete) occurred in patients previously unresponsive to r-EPO alone. All erythroid responses disappeared, once combined therapy was stopped. Concomitant adverse effects included general malaise (1 patient), fever (1 patient) and skin infection (1 patient). Furthermore, a frank leukemic evolution was observed during the course of the treatment in 2 patients ( 1 RAEB-T and 1 RAEB secondary to autologous stem cell tranplantation for multiple myeloma). In another patient with RAEB-T, marrow blast ceil count decreased from 25% to 12% under combined therapy. One of patients with complete erythroid response died of pneumonia with hemorrhagic complications some weeks after the interruption of combined therapy. Our preliminary results indicate that the combination of amifostine and r-EPO may improve cytopenia (and, in particular, anemia) in some patiens with MDS. Continuative therapy seems to be necessary to maintain the response.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART II
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hematology

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