Accidental busulfan overdose during conditioning for stem cell transplantation.

High dose busulfan is widely used in preparative regimens for bone marrow transplantation. We describe three cases of accidental busulfan overdosing. Two adults received a single dose of 8 and 18 mg/kg busulfan, respectively. Doses of 9 x 4 mg/kg were ingested by a 14-year-old girl, who experienced seizures. In all cases, no severe liver toxicity including veno-occlusive disease was observed. Plasma samples were obtained from two patients. Busulfan plasma concentrations were far above published values after high-dose busulfan treatment. Busulfan was eliminated by a first-order process. All patients survived these high doses of busulfan and successful transplantation was possible. Two patients died from refractory GvHD on days 91 and 80 after transplantation. One patient is alive in remission after an observation time of 18 months. These cases show that busulfan overdosing may occur and pharmacokinetic evaluation is warranted to estimate risk of early and late toxicity.

Bone marrow transplantation after lethal chemotherapy in "nude" mice.

Isogenic bone marrow transplantation was performed in "nude" and normal C3H mice after lethal doses of dimethylmyleran (DMM), meso-DMM, and (+/-) DMM were given. Nude mice were not more sensitive to DMM or its isomers than normal mice. With adequate cell doses in the range of 3 X 10(6) to 30 X 10(6) bone marrow cells or 10 X 10(6) to 30 X 10(6) spleen cels, the survival rate after lethal chemotherapy was not significantly different between nude mice reconstituted with a graft from nude donors and normal mice reconstituted with a graft from normal donors. Only with suboptimal cell dose (1 X 10(6) bone marrow cells) was survival superior in normal mice. Thinsic factor. Nude mice accepted also bone marrow grafts from allogeneic nude donors.

Accidental busulfan overdose: enhanced drug clearance with hemodialysis in a child with Wiskott-Aldrich syndrome.

A 4.6 kg infant with Wiskott-Aldrich syndrome received an accidental overdose of busulfan during preparation for allogeneic stem cell transplantation. Pharmacokinetic analysis of plasma busulfan levels alerted staff to the dosing error. Hemodialysis was immediately performed and resulted in accelerated clearance of busulfan. There were no acute neurologic and hepatic side-effects of the busulfan overdose, and despite 2 months of cough accompanied by rales, the patient is now free of pulmonary symptoms. Stable partial donor chimerism occurred after transplantation. At present, the patient is thriving and infection-free 12 months after transplantation, although his platelet count remains at the lower limit of normal.