Phase II study of busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for allogeneic bone marrow transplantation in patients with advanced myeloid malignancies.
A previous phase I dose escalation study determined that the maximum tolerated doses of busulfan and cyclophosphamide that could be combined with 12.0 Gy of total body irradiation were 7 mg/kg and 50 mg/kg, respectively. A phase II study of these three agents was carried out in 56 patients with advanced myeloid malignancies receiving allogeneic bone marrow transplants from HLA-identical donors. Cyclosporine with methotrexate or with prednisone was administered for prophylaxis against graft-versus-host disease. Grade 3 (n = 8) and 4 (n = 3) regimen-related toxicity occurred in 20% of patients, which was the maximum predicted from the phase I study. The 2-year actuarial probabilities of non-relapse mortality and relapse were 0.52 and 0.55, respectively. Fourteen patients survive, 12 in remission, 581-1761 days post-transplant. The actuarial probabilities of disease-free survival for patients with recurrent acute myeloid leukemia and advanced chronic myeloid leukemia at 2 years were 20% and 23%, respectively. When compared with our historical experience in patients receiving other treatment regimens, there was no apparent improvement in disease-free survival.
Lynch
M H
MH
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Petersen
F B
FB
Appelbaum
F R
FR
Bensinger
W I
WI
Clift
R A
RA
Storb
R
R
Sanders
J E
JE
Hansen
J A
JA
Buckner
C D
CD
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide; D002066:Busulfan