Birgitta Versluijs

29 Pulmonary complications of childhood cancer treatment Pulmonary complications of chemotherapy There is a paucity of literature on late onset chemotherapy induced pulmonary disease, and most reports date from the 1980s and 1990s. The agents associated with lung toxi- city include bleomycin, alkylating agents (such as busulphan and cyclophosphamide), and nitrosureas (BCNU and CCNU). 6,7,11,17,18 Bleomycin is an antibiotic agent with antitumor activity by inducing free radicals. It is mainly applied in children with germcell tumours or Hodgkin’s disease. Bleomycin is poorly metabolized in the lung because of low levels of the bleomycin detoxifying en- zyme bleomycin hydrolase. Accumulation of the drug leads to vascular and cell damage, inducing an inflammatory process with influx of macrophages and fibroblasts in lung parenchyma, ultimately leading to lung fibrosis. 18–20 Pulmonary toxicity of bleomycin increases with impaired renal function at the time of administration, the cumulative dose and concomitant thoracic irradiation or administration of other chemotherapeutic agents. 11,19–21 Bleomycin induced pneumonitis is a severe and sometimes fatal complication. It usually starts gradually during or early after treatment. Patients have non-productive cough and exertional dyspnoea, sometimes progressing to dyspnoea at rest and cyanosis. Cortico- steroids can be considered, but most important is that further bleomycin administration is withheld. 20 Lung fibrosis has been reported in 10% of adults treated with bleomycin above a thres- hold dose of 400 units/m 2 . 18,21,22 For these doses there are no data in children. In a study by De et al. 23 at least one PFT abnormality was present in 52.2% of patients with a me- dian follow up of 3.9 years after bleomycin treatment (median cumulative dose of only 65 units/m 2 ). Obstructive lung disease and hyperinflation were the most common PFT abnormalities, but only a minority of survivors were symptomatic. 23 It has been suggested that oxygen therapy may exacerbate bleomycin induced lung toxi- city. 11,19 In a large cohort study of bleomycin-exposed patients undergoing surgery, howe- ver, Aakre et al. 24 showed that smoking habits, preoperative PFT and fluid management during the procedure were more important risk factors for postoperative acute respirato- ry distress syndrome than supplemental oxygen administration. Others have confirmed that the risk for late deterioration of lung function due to high oxygen. exposure (either during anaesthesia or scuba diving) in bleomycin exposed survivors is negligible as long as PFTs are normal and exposure occurred more than one year prior. 21,25 2