Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial.
Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy.
Petersen
F B
FB
Department of Medicine, University of Washington, School of Medicine, Seattle.
Deeg
H J
HJ
Buckner
C D
CD
Appelbaum
F R
FR
Storb
R
R
Clift
R A
RA
Sanders
J E
JE
Bensinger
W I
WI
Witherspoon
R P
RP
Sullivan
K M
KM
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008223:Lymphoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D014916:Whole-Body Irradiation
D003037:Cobalt Radioisotopes; D003520:Cyclophosphamide