Hd

Requires activation to reactive intermediates (methyl-carbonium ions) that alkylate nucleic acids; thus, DNA, RNA, and protein synthesis is inhibited

Acute

■ Severe nausea/vomiting (onset 1-2 h, may last up to 12 h16)

■ Myelosuppression (mild); (onset 7 days, recovery 21-28 days)

■ Anaphylactic reactions

■ Photosensitivity

■ Flu-like syndrome (may last several days after infusion17)

■ Extravasation (irritant) Chronic

■ Hepatocellular necrosis

"DLT = dose-limiting toxicity.

"DLT = dose-limiting toxicity.

higher doses, such as those used in stem cell transplant regimens, adverse effects become more severe. Mild nausea and vomiting may occur. In addition, because of its ability to readily penetrate the CNS, busulfan can lower the seizure threshold, causing generalized tonic-clonic seizures.12 For this reason, prophylactic antiepileptic medications are commonly administered. Veno-occlusive disease, or VOD, is thought to be associated with high doses of busulfan.12 Finally, pulmonary toxicity can occur. "Busulfan lung" is characterized by pulmonary fibrosis and presenting symptoms include nonproductive cough, shortness of breath, and weight loss.51219 This complication may correlate with duration of busulfan therapy, with a higher incidence occurring in those who have received greater than 3 years of treatment. It is often fatal, with average survival of 5 months after diagnosis.19

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