RAPID COMMUNICATION Stimulation of Hematopoiesis by Amifostine in Patients With Myelodysplastic Syndrome

The aminothiol, amifostine (Ethyol; U.S. Bioscience, West with the three-times-a-week dose schedule. Fourteen paConshohocken, PA), is a cytoprotective agent that ameliotients had a 50% or greater increase in absolute neutrophil rates the toxicities of anticancer therapy. In vitro, amifostine count with amifostine treatment (range, 426 to 11,348/mL). promotes the formation and survival of primitive hematoPlatelet count increased in 6 (43%) of 14 patients with thrompoietic progenitors derived from myelodysplastic bone marbocytopenia (absolute increase, 16,000 to 110,000/mL), and row (BM) specimens. To evaluate the hematological effects 5 of 15 red blood cell transfusion-dependent patients had a of amifostine, 18 patients with myelodysplastic syndrome 50% of greater reduction in transfusion needs. Assayable (MDS) and one or more refractory cytopenias received treathematopoietic progenitors increased in 13 of 15 evaluable ment with amifostine in a Phase I/II study. Four cohorts patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM received intravenous treatment with 100, 200, or 400 mg/ (6). Amifostine doses less than or equal to 200 mg/m were m amifostine three times a week, or 740 mg/m weekly for well tolerated, whereas grade II nausea, vomiting, and fathree consecutive weeks followed by 2 weeks observation. tigue was limiting at higher doses. Three patients with exNonresponding patients received a second course of therapy cess blasts before enrollment experienced an increase in BM at the next higher dose level depending upon drug tolerance. blast percentage and two patients had evolution to acute Bone marrow (BM) progenitor growth was assessed before leukemia that persisted after treatment withdrawal. We contreatment and after day 21. Diagnoses included refractory clude that amifostine administered at doses Ù200 mg/m anemia (7), refractory anemia with ringed sideroblasts (5), three times a week is well tolerated and has hematologic refractory anemia with excess blasts (RAEB) (4), and RAEBactivity in patients with MDS. in transformation (RAEB-t) (2). Singleor multi-lineage heq 1997 by The American Society of Hematology. matologic responses occurred in 15 patients (83%) treated