Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study.
Thirty-seven patients with advanced hematologic malignancy were entered into a phase I study designed to define a maximum tolerable dose (MTD) of etoposide (VP-16) and cyclophosphamide (CY) combined with 12 Gy fractionated total body irradiation (TBI) as preparation for marrow transplantation from an HLA-identical sibling (n = 13) or with cryopreserved autologous marrow (n = 24). Dose levels ranged from 36 mg/kg of VP-16 combined with 67 mg/kg of CY to 52 mg/kg of VP-16 combined with 103 mg/kg of CY followed by 12 Gy TBI. The MTD for allogeneic marrow recipients was 36 mg/kg of VP-16 + 52 mg/kg of CY followed by 12 Gy TBI and for autologous marrow recipients 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI. Pulmonary and liver toxicities were dose limiting. All of 31 evaluable patients transplanted in relapse achieved a complete remission. However, in all but three of these patients the disease relapsed 28-899 (median 110) days post-transplant. Currently, six of 24 autologous marrow recipients are surviving, three in remission 256, 340 and 764 days post-transplant. None of 12 allogeneic marrow recipients have survived. In conclusion, a preparative regimen combining 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI is well tolerated by autologous marrow recipients and 36 mg/kg VP-16 + 67 mg/kg CY followed by 12 Gy TBI is well tolerated by allogeneic marrow recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
F B
FB
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Buckner
C D
CD
Appelbaum
F R
FR
Sanders
J E
JE
Bensinger
W I
WI
Storb
R
R
Deeg
H J
HJ
Witherspoon
R P
RP
Sullivan
K M
KM
Clift
R A
RA
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery*; D008223:Lymphoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery*; D008875:Middle Aged; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D005047:Etoposide; D003520:Cyclophosphamide