Preliminary Data on Once-Daily IV Busulfan at 3.2 mg/kg/day Indicate That It Is Safe as a Component of the Conditioning Regimen for Hematopoietic Stem Cell Transplantation.

Busulfan is a useful chemotherapy in many stem cell transplant regimens. Data support the use of buslfan in transplant patients, especially if they have had prior treatment with radiation therapy. The dose of the busulfan used in myloablative stem cell transplantation has traditionally been sixteen oral doses of 1mg/kg/dose. The oral dosing has been limited by unreliable oral absorption of busulfan tablets. Transplant related mortality and incidence of venocclusive disease are directly related to high peak levels of busulfan. Relapse has been associated with low peak levels of busulfan.

Recently, busulfan has become available as an IV preparation and preliminary data indicate that the peak busulfan levels are predictable via the IV administration route. The bulk of the data available on outcomes after transplantation using IV busulfan have used a QID dosing schedule of 0.8mg/kg/dose for sixteen doses. A smaller data base has utilized IV busulfan for stem cell transplantation as a single daily dose of 3.2mg/kg/day for 2–4 days. We present data on 19 patients treated at RMBMTP for hematological malignancies with the 3.2mg/kg/day dosing for stem cell transplantation. Sixteen of the 19 patients underwent allogeneic stem cell transplantation from related or unrelated donors from April 2003 to March 2004. Three patients underwent autologous stem cell transplants using the IV busulfan 3.2 mg/kg/day with cyclophosphamide 120 mg/kg total dose. None of the autologous transplant patients developed VOD or death during the first 100 days. 8 of the 16 patients undergoing allogeneic stem cell transplant have died: 4 patients died of relapsed disease, 2 died of GVHD, 1 patient died of sepsis, and 1 died of GVHD, relapse and a fungal infection. No autologous or allogeneic stem cell transplant patients died of regimen related toxicity.

This single daily dose regimen has been well tolerated with no increase in transplant related mortality or VOD. The 3.2 mg/kg/day dose appears adequate to assure engraftment of allogeneic stem cells. The patients presented had high-risk hematological malignancies. Although the followup is short, the OS survival of 100% for the autologous stem cell transplants and 50% for the allogeneic stem cell transplantation is consistent with published data for transplantation of high-risk hematological malignancies. There does not appear to be a higher transplant related mortality, GVHD or VOD rate for patients treated with busulfan at 3.2 mg/kg/day as a single dose.