Cytoprotection by amifostine during autologous stem cell transplantation for advanced refractory hematologic malignancies.
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.
Gabriel
Don A
DA
Division of Hematology/Oncology, Bone Marrow Transplant Program, University of North Carolina, Chapel Hill, North Carolina 27599, USA. laser@med.unc.edu
Shea
Thomas C
TC
Serody
Jonathan S
JS
Moore
Dominic T
DT
Kirby
Suzanne L
SL
Harvey
Donald
D
Krasnov
Carol
C
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
D019653:Myeloablative Agonists; D009294:Narcotics; D011837:Radiation-Protective Agents; D004999:Amifostine