Prior Bleomycin Exposure
Background
-
Bleomycin (BLM) is an antitumor antibiotic used to treat mostly germ cell tumors and Hodgkin lymphomas
-
Mechanism of action: works by inducing breaks in DNA through a complex of bleomycin, ferrous iron and oxygen
-
BLM is inactivated in the body by BLM-hydrolase (BLM-h)
-
BLM-h activity is lowest in skin and lungs
-
Skin and lungs are the organs most susceptible to BLM toxicity
-
-
Pathophys. of toxicity is poorly understood but likely through a combination of:
-
Oxidative damage via oxygen free radicals
-
Relative deficiency of BLM-h
-
Genetic susceptibility
-
Subsequent inflammatory cascade
-
-
80% renally cleared
Bleomycin-Induced Lung Injury
-
Life-threatening interstitial pulmonary fibrosis AKA BLM-induced lung injury
-
Signs and Symptoms:
-
Dyspnea (earliest sx), cough, chest pain, crackles
-
Chest opacities on CXR
-
Asymptomatic decline in DLCO
-
-
Develops subacutely, over days to weeks, within 1-6 months of bleomycin exposure
-
Assess PFTs
-
↓ DLCO
-
Restrictive pattern: ↓ FVC, TLC and FRC
-
-
Co-morbid conditions:
-
Testicular or ovarian germ cell tumor
-
Ovarian sex cord-stromal tumor
-
Hodgkin lymphoma
-
-
Risk factors:
-
↑ age
-
Renal insufficiency
-
↑ cumulative drug dose (rare if dose exceeds 270 IU)
-
Severity of underlying malignancy
-
↑ FiO2 use
-
Concomitant radiation therapy (i.e. thoracic irradation)
-
Treatment with other chemo agents (i.e. cisplatin)
-
Cigarette Smoking
-
Goals
-
Avoid exposure to high FiO2
-
Evidence is largely anecdotal
-
High FiO2 even years after BLM exposure can increase risk for BLM-induced lung injury
-
If hypoxemic, titrate minimal amount of oxygen to maintain O2 sat 89-92%
-
-
Minimize IV fluids to avoid volume overload
References
-
Limper, AH. (2022) Chapter 99: Drug-Induced Pulmonary Disease. In Murray & Nadel's Textbook of Respiratory Medicine, 7th Ed. p1378-1394.e16