Etoposide with without G-CSF with busulfan and cyclophosphamide as conditioning for bone marrow transplantation

To increase the efficacy of bone marrow transplantation (BMT), we have tried to add etoposide (VP-16) to busulfan/cyclophosphamide (BU/CY). Twelve patients received 16 mg/kg of BU and 120 mg/kg of CY with 15-30 mg/kg of VP-16. Another two patients received 5 mu g/kg of G-CSF with 30 mg/kg of VP-16. Patients tolerated escalating doses of VP-16 without any significant hepatotoxicity. Their maximal level of bilirubin was 37.6 mu mol/L (2.2 mg/dl), and there was no significant skin toxicity or mucositis. By contrast, two patients who received G-CSF with 30 mg/kg of VP-16 developed hyperbilirubinemia and veno-occlusive disease, which terminated this phase I study. VP-16 can be safely combined with BU/CY less than or equal to 30 mg/kg in three divided doses, and its effect on survival should be evaluated. G-CSF added to this regimen, however, should be used with great caution. (C) 1996 Wiley-Liss, Inc.