Lack of cytoprotective effect of amifostine following HLA-identical sibling transplantation for advanced myelodysplastic syndrome (MDS): a pilot study.
The objective of this prospective study was to determine whether amifostine (Ethyol) reduced conditioning-related toxicity following a regimen of busulfan (7 mg/kg) and fractionated total body irradiation (6 x 200 cGy). In all, 12 patients with advanced myelodysplastic syndrome transplanted from HLA-identical siblings were enrolled. Patients received 340 mg/m(2) amifostine i.v. twice daily during conditioning (days -7 through -1). All patients developed oropharyngeal mucositis. Six patients had evidence of sinusoidal obstruction syndrome of the liver. Six patients experienced pulmonary toxicity of grades II-III. A total of 11 patients died, one with relapse and 10 with infectious complications or regimen-related toxicity. Nonrelapse causes of death included invasive aspergillosis in three, multiorgan failure in three, and idiopathic interstitial pneumonitis in two patients. One patient each died of organizing pneumonia and CMV pneumonia. One patient is alive in complete remission 31 months after transplantation. These results were not superior to those in patients conditioned with busulfan plus fractionated total body irradiation and not given amifostine, and suggest that amifostine, as administered here, has no protective effect against toxicity from this myeloablative regimen.
Benesch
M
M
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
McDonald
G B
GB
Schubert
M
M
Appelbaum
F R
FR
Deeg
H J
HJ
D000328:Adult; D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D002423:Cause of Death; D019610:Cytoprotection / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000401:mortality / Q000628:therapy*; D010865:Pilot Projects; D035781:Siblings; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D002066:Busulfan; D004999:Amifostine