Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study
Petersen, F.B.; Buckner, C.D.; Appelbaum, F.R.; Sanders, J.E.; Bensinger, W.I.; Storb, R.; Deeg, H.J.; Witherspoon, R.P.; Sullivan, K.M.; Clift, R.A.
Bone Marrow Transplantation 10(1): 83-88
1992
ISSN/ISBN: 0268-3369 PMID: 1515884 Document Number: 400001
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. Further studies of the anti-leukemia efficacy of this regimen are warranted and may be the most informative when carried out in patients with less advanced disease at the time of transplant.