A 62-year-old male undergoing bleomycin-containing ABVD chemotherapy for Hodgkin lymphoma develops progressive dyspnea and bibasilar crackles on examination. CT chest shows ground-glass opacities and subpleural fibrosis. The dose-limiting toxicity of bleomycin is:

• A Nephrotoxicity from renal tubular accumulation of bleomycin
• B Cardiac toxicity from bleomycin-induced myocarditis
• C Hepatotoxicity from bleomycin-induced sinusoidal obstruction syndrome
• D Pulmonary toxicity due to free radical-mediated lung injury ✓

Explanation

Bleomycin's dose-limiting toxicity is pulmonary toxicity (pneumonitis progressing to fibrosis), occurring in 10–40% of patients treated with cumulative doses above 400 units. The lung is particularly vulnerable because it lacks bleomycin hydrolase, the enzyme that inactivates bleomycin in most tissues. Bleomycin-iron complexes generate superoxide and hydroxyl radicals that cause DNA strand breaks in pulmonary endothelial and epithelial cells. Risk is increased by high cumulative dose, age > 70, renal impairment, and concurrent oxygen therapy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.