Once-daily intravenous busulfan as myeloablative, reduced-toxicity conditioning regimen: results in young and adult patients with hematological malignant and nonmalignant diseases

Postulating favorable antileukemic effect with reduced toxicity and improved safety, we used intravenous busulfan (BU) associated with either cyclophosphamide (CY) or fludarabine (FLU) as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) in young (n=4; median age 3 years, range 9 months to 6 years) and adult (n=9; median age 54 years, range 22 to 61 years) patients with hematological diseases between May 2006 and June 2008. Two patients were females and 11 were males. Seven patients were affected by acute myeloid leukemia (AML) (6 in first complete remission (CR) and 1 in second CR), 4 by myelodisplastic syndrome, 1 by acute lymphoblastic leukemia (ALL) and 1 by thalassemia major. Eight patients received FLU at a dose of 30 mg/m2/day for 4 days (from -5 to -2) given over 60 minutes, immediately followed by BU given in single intravenous administration over 3 hours at a dose of 3,2 mg/kg day for 4 days (total dose 12,8 mg/kg). Five patients received the same dosage of BU from day -7 to day -4 followed by CY 60 mg/Kg/day from -3 to -2. Six donors were HLA-identical siblings, 1 donor was 1 antigen mismatched sibling and 6 were HLA-matched unrelated (MUD). The graft-versus-host disease (GvHD) prophylaxis included cyclosporine and short course methotrexate for all patients with the addition of antithymocyte globulin for the 6 patients transplanted from MUD. Ten patients received bone marrow cells (median dose of nucleated cells 3,76x108/kg, range 3,1- 10,9) and 3 were given peripheral blood stem cells (median dose 7,4 x106/kg CD34+, range 5,7-7,7). All patients achieved primary engraftment. The median time to 0.5x109/L neutrophils and 25x109/L platelets was 18 days (range, 15-32) and 15 days (range, 12-25) respectively.