Use of amifostine in hematologic malignancies, myelodysplastic syndrome, and acute leukemia.
The phosphorylated thiol amine, amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), is a cytoprotective agent for cisplatin-based chemotherapy. Recent investigations have given rise to new potential applications of amifostine in hematologic malignancies. Amifostine appears to exert a sustained mitogenic effect in primitive hematopoietic progenitors that results in a significant increase in colony-forming capacity. Amifostine also retards cell loss and delays commitment to apoptosis initiated by cytokine deprivation, suggesting that amifostine has trophic effects similar to the hematopoietic cytokines. The abilities to prolong progenitor survival and to delay apoptosis under conditions of cellular stress make amifostine an attractive agent for investigation in bone marrow failure states. Amifostine promotes more effective hematopoiesis in patients with myelodysplastic syndrome, although additional investigation is needed to further define the optimal dose and schedule of administration. Furthermore, amifostine may selectively enhance the cytotoxicity of chemotherapeutic agents in leukemia progenitors. When the sensitivity of leukemic and normal progenitors to mafosfamide was evaluated with and without amifostine pretreatment, amifostine effectively protected normal myeloid and erythroid progenitors while increasing leukemic cell kill. Thus, amifostine represents a unique agent with promising potential for therapeutic application in hematologic malignancies. Further investigation is needed to define its role in clinical practice.
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Bone Marrow Transplant Program, Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA.
D000208:Acute Disease; D004999:Amifostine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D019610:Cytoprotection; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006412:Hematopoietic Stem Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008624:Mercaptoethylamines / Q000737:chemistry; D015394:Molecular Structure; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013095:Spermidine / Q000737:chemistry; D013096:Spermine / Q000737:chemistry
D008624:Mercaptoethylamines; D020011:Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D013096:Spermine; D004999:Amifostine; C045611:WR 33278; D013095:Spermidine