Lung Fibrosis 10 Years after Cessation of Bleomycin Therapy

Abstract

Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain types of squamous-cell carcinoma. The common adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up to 46% of patients treated with BLM-containing chemotherapy and lung toxicity usually appears during treatment. Here we describe a patient with lung fibrosis, who presented with slow progressive breathlessness and pneumothorax more than 10 years after cessation of BLM therapy. A 15 yearold girl presented with abnormal shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region at 1 year of age and obtained complete remission after being treated with tumor resection, radiation, and several anti-cancer drugs including BLM. There were no abnormal findings in chest X-ray until she reached 3 years of age, when she had developed respiratory distress that worsened with age. The patient had experienced an episode of pneumothorax at 13 years of age. Chest CT at the time revealed interstitial reticular opacities. Radiological findings and pathological examination of the lung tissue obtained during bullectomy with video-assisted thoracic surgery were compatible with BLM-induced pneumonitis. The present study suggests that lung fibrosis may surface more than 10 years after cessation of BLM therapy at the age of 1 year, with no chest radiographic findings 1 year after completion of chemotherapy. The use of BLM in infants requires strict supervision and observation and careful long-term follow up. Bleomycin; child; pneumonitis; pneumothorax Tohoku J. Exp. Med., 2008, 216 (1), 77-80. © 2008 Tohoku University Medical Press Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain squamous-cell carcinoma. Most significant adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis.

Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant,N-acetyl-l-cysteine, and novel thiol antioxidant,N,N′-bis-2-mercaptoethyl isophthalamide

“…Bleomycin is an oxidant chemotherapeutic drug that is widely used to induce experimental lung fibrosis in animal models (Jackson, 1985; Tashiro et al 2008; Fang, 2000). Iron and iron-redox are thought to play a key step in bleomycin-induced ROS production (Burger et al 1979; Antholine et al 1981).…”

Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma

“…Patients with BILI present initially with a nonproductive cough, exertional dyspnea, and sometimes fever. These clinical manifestations of BILI are generally encountered weeks to months after the initiation of treatment, but the development of BILI up to 2–10 years after discontinuation of bleomycin therapy has also been reported [ 7 , 8 ]. Due to the absence of clinical, radiological, or pathologic findings specific to BILI, its diagnosis is generally made by a combination of 1) the exclusion of other etiologies that may cause lung involvement, and 2) radiologic and functional findings compatible with BILI.…”

Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

“…All subjects knew the aim of the study and gave their informed consent. e study was conducted in accordance with the declaration of Helsinki (1964) and was approved by the Internal Review Board of the University of Lyon [11][12][13][14][15][16][17][18][19][20]. e control group was composed of patients who underwent pulmonary tests as part as their routine medical followup, and whom results were 00% ± 0% of the normal predicted values.…”

“…Bleomycin (BLM) is another agent known for its pulmonary toxicity [8][9][10][11][12][13]. is cytotoxic agent is successfully used in the treatment of several malignancies such as germ cell tumors, lymphomas, and some squamous cell carcinomas.…”

“…BLMinduced pneumonitis occurs in around 46% of patients treated with a BLM-based chemotherapy. is lung toxicity usually appears during treatment [13] but can also appear up to 10 years aer the incriminated treatment. Mulder et al studied a cohort of childhood cancer survivor who received a BLM-based chemotherapy.…”