title: Cytoprotection by amifostine during autologous stem cell transplantation for advanced refractory hematologic malignancies.
abstract: This study evaluated whether amifostine protects against mucositis and other toxicities in patients with advanced, refractory, or recurrent hematologic malignancies undergoing high-dose chemotherapy and total body irradiation. Thirty-five patients (20 with non-Hodgkin lymphoma, 12 with Hodgkin disease, and 3 with acute myelogenous leukemia) who underwent autologous stem cell transplantation were conditioned with total body irradiation 2 Gy twice daily on days -8 through -6; cyclophosphamide 6 g/m(2), etoposide 1.8 g/m(2), and carboplatin 1 g/m(2) on days -5 through -3; and amifostine 500 mg/m(2) on days -8 through -2. Prior institutional experience in patients treated without amifostine was used as a historical comparison (no-amifostine group). Severe mucositis occurred in 14 (40%) of 35 patients in the amifostine group, compared with 33 (94%) of 35 in the no-amifostine group (P < .0001). Total parenteral nutrition was used by 4 (11%) of 35 amifostine-treated patients and 34 (97%) of 35 no-amifostine patients (P < .0001). The median duration of narcotic use decreased from 15.5 days with no amifostine to 11 days with amifostine (P = .002). Granulocyte and platelet engraftment times were similar. Prospective trials with innovative designs and clearly defined stopping rules are warranted to confirm whether amifostine reduces the toxicities of a myelosuppressive conditioning regimen before autologous stem cell transplantation without compromising therapeutic response.
authors.affiliation: Division of Hematology/Oncology, Bone Marrow Transplant Program, University of North Carolina, Chapel Hill, North Carolina 27599, USA. laser@med.unc.edu
authors.forename: Don A
authors.initials: DA
authors.lastname: Gabriel
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Kirby
authors.forename: Donald
authors.initials: D
authors.lastname: Harvey
authors.forename: Carol
authors.initials: C
authors.lastname: Krasnov
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006689:Hodgkin Disease / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage; D010288:Parenteral Nutrition / Q000379:methods; D011446:Prospective Studies; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D019653:Myeloablative Agonists; D009294:Narcotics; D011837:Radiation-Protective Agents; D004999:Amifostine