Busulphan given as four single daily doses of 150 mg/m2 is safe and effective in children of all ages.
We examined the effects of busulphan (BU) dose and patient age on toxicity and outcome in 63 children with acute leukaemia given BUCY prior to allogeneic or autologous BMT. BU was administered as four single daily oral doses, based either on weight (4 x 4 mg/kg) or surface area (4 x 150 mg/m2). BU pharmacokinetic analysis was not used to dose adjust. The average daily (mg/kg) BU dose was 43% higher for the group given 150 mg/m2 compared to the 4 mg/kg dose group. This produced a median BU AUC 61% higher than with the 4 mg/kg dose. Only one child did not achieve full allogeneic donor engraftment. Regimen-related toxicity was low. Although younger children had faster BU clearance, the 4 x 150 mg/m2 dose ensured equivalent systemic exposure to BU, and resulted in a high frequency of engraftment without a significant increase in serious toxicity. BU, given as four single daily doses of 150 mg/m2, is appropriate and safe in all age groups of children. Given the reliable pharmacokinetics, low toxicity and high rate of allogeneic engraftment, there is no need for routine pharmacokinetic monitoring or dose modifications. This dosage regimen may be applicable for use with i.v. BU.
Shaw
P J
PJ
Department of Oncology, The Children's Hospital at Westmead, NSW, Australia. Peters@chw.edu.au
Nath
C
C
Berry
A
A
Earl
J W
JW
D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000601:surgery*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000601:surgery*; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D002066:Busulfan