Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels

Amifostine increases in vitro burst-forming unit-erythroid and colony-formi ng unit-granulocyte/granulocyte-macrophage cultured from bone-marrow cells from patients with myelodysplastic syndrome (MDS). Several small clinical s tudies give divergent informations about the potential of amifostine as sin gle agent to improve hematopoiesis in MDS patients. In these studies, patie nts with refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-T) were analyzed together, resulting in response ra tes varying from 8% to 30%. The present multi-center study evaluated whethe r treatment with amifostine is of clinical benefit in patients with RA who are transfusion dependent. The effect on transfusion frequency as well as o n platelets and absolute neutrophil count (ANC) was examined in 14 patients with RA [median age 67 years (55-72 years), male:female 9:5]. Four treatme nt cycles were planned, each consisting of intravenous amifostine at 200 mg /m(2)/day three times per week followed by a 2-week interval. Since tumor n ecrosis factor (TNF)alpha is a main suppressive cytokine for hematopoiesis in RA patients, serum samples for analyzing endogenous levels of TNF alpha were collected prior to the study and after four treatment cycles. In three patients (21%), reduced transfusion requirement with prolongation of the t ransfusion interval from 4 weeks to 8 weeks (two patients) and 4 weeks to 6 weeks was seen. An increase in ANC from 400/mu l to 2600/mu l and 200/mu l to 3400/mu l was observed in two patients. Platelets increased from 129,00 0/mu l to 277,000/mu l in an additional patient. In one patient, disease pr ogression from RA to RAEB was observed. Serum TNF alpha levels were increas ed in MDS patients compared with normal controls (18.8 pg/ml vs 9.1 pg/ml), and there was no change during the treatment with amifostine (17.5 pg/ml). In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA. The serum TNF alpha levels were unchanged duri ng treatment with amifostine in RA patients.