Bleomycin-induced lung injury
- Darren Feldman, MD
Darren Feldman, MD
- Assistant Attending Physician,
- Department of Medicine,
- Memorial Sloan Kettering Cancer Center
- Assistant Professor in Medicine,
- Weill Cornell Medical College
- Nicholas Vander Els, MD
Nicholas Vander Els, MD
- Assistant Professor of Medicine
- Cornell University Medical College
- Section Editor
- Philip W Kantoff, MD
Philip W Kantoff, MD
- Section Editor — Testicular Cancer
- Chairman of Medicine
- Memorial Sloan Kettering Cancer Center
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- Diane MF Savarese, MD
Diane MF Savarese, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Oncology and Palliative Care
- Clinical Instructor of Medicine
- Harvard Medical School
Bleomycin is an antitumor antibiotic that was isolated from a strain of Streptomyces verticillus in 1966 . It has been used successfully to treat a variety of malignancies, predominantly germ cell tumors and Hodgkin lymphoma. The major limitation of bleomycin therapy is the potential for life-threatening interstitial pulmonary fibrosis (also called fibrosing alveolitis) in up to 10 percent of patients receiving the drug [2-5]. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis .
The pathogenesis and clinical aspects of bleomycin-induced lung injury will be reviewed here. Potential drug interactions that may modify the course of bleomycin-induced lung injury and the therapeutic options available for management will also be discussed. A general approach to immunocompromised patients with respiratory symptoms and the evaluation of interstitial lung disease in patients receiving chemotherapy are presented separately. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates" and "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment".)
The antineoplastic effect of bleomycin is unique among anticancer agents, and is thought to involve the production of single- and double-strand breaks in DNA (scission) by a complex of bleomycin, ferrous ions, and molecular oxygen [2,6,7]. Bleomycin binds to DNA by intercalation of the bithiazole moiety between base pairs of DNA and by electrostatic interactions of the terminal amines. The reduction of molecular oxygen by ferrous ions chelated by bleomycin leads to hydrogen subtraction from the C3 and C4 carbons of deoxyribose, resulting in cleavage of the C3-C4 bond and liberation of a base with a DNA strand break . Bleomycin is inactivated in vivo by the enzyme bleomycin hydrolase, a cytosolic aminopeptidase that has lower activity in the skin and lungs.
The mechanism of bleomycin-induced lung injury is not entirely clear, but likely includes components of oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and elaboration of inflammatory cytokines.
Oxidative damage to the lung appears important in the pathophysiology of lung injury, and antioxidants may ameliorate the process [4,8]. Depletion of iron with chelators also reduces the toxicity of bleomycin both in vitro and in vivo, probably secondary to decreased production of free radicals [4,9,10].
- Meadors M, Floyd J, Perry MC. Pulmonary toxicity of chemotherapy. Semin Oncol 2006; 33:98.
- Jules-Elysee K, White DA. Bleomycin-induced pulmonary toxicity. Clin Chest Med 1990; 11:1.
- Camus P. Interstitial lung disease from drugs, biologics, and radiation. In: Interstitial Lung Disease, 5th ed, Schwarz MI, King TE Jr (Eds), People's Medical Publishing House, Shelton, CT 2011. p.637.
- Sleijfer S. Bleomycin-induced pneumonitis. Chest 2001; 120:617.
- O'Sullivan JM, Huddart RA, Norman AR, et al. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol 2003; 14:91.
- Sikic BI. Biochemical and cellular determinants of bleomycin cytotoxicity. Cancer Surv 1986; 5:81.
- Chandler DB. Possible mechanisms of bleomycin-induced fibrosis. Clin Chest Med 1990; 11:21.
- Fantone JC, Phan SH. Oxygen metabolite detoxifying enzyme levels in bleomycin-induced fibrotic lungs. Free Radic Biol Med 1988; 4:399.
- Martin WJ 2nd, Kachel DL. Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species. J Lab Clin Med 1987; 110:153.
- Chandler DB, Barton JC, Briggs DD 3rd, et al. Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster. Am Rev Respir Dis 1988; 137:85.
- Lazo JS, Merrill WW, Pham ET, et al. Bleomycin hydrolase activity in pulmonary cells. J Pharmacol Exp Ther 1984; 231:583.
- Harrison JH Jr, Lazo JS. Plasma and pulmonary pharmacokinetics of bleomycin in murine strains that are sensitive and resistant to bleomycin-induced pulmonary fibrosis. J Pharmacol Exp Ther 1988; 247:1052.
- Harrison JH Jr, Hoyt DG, Lazo JS. Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice. Mol Pharmacol 1989; 36:231.
- Hoyt DG, Lazo JS. Murine strain differences in acute lung injury and activation of poly(ADP-ribose) polymerase by in vitro exposure of lung slices to bleomycin. Am J Respir Cell Mol Biol 1992; 7:645.
- Filderman AE, Genovese LA, Lazo JS. Alterations in pulmonary protective enzymes following systemic bleomycin treatment in mice. Biochem Pharmacol 1988; 37:1111.
- Phan SH, Kunkel SL. Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp Lung Res 1992; 18:29.
- Piguet PF, Collart MA, Grau GE, et al. Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. J Exp Med 1989; 170:655.
- Ortiz LA, Lasky J, Hamilton RF Jr, et al. Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. Exp Lung Res 1998; 24:721.
- Ballinger MN, Newstead MW, Zeng X, et al. IRAK-M promotes alternative macrophage activation and fibroproliferation in bleomycin-induced lung injury. J Immunol 2015; 194:1894.
- Schrier DJ, Phan SH, McGarry BM. The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis. A biochemical evaluation. Am Rev Respir Dis 1983; 127:614.
- Helene M, Lake-Bullock V, Zhu J, et al. T cell independence of bleomycin-induced pulmonary fibrosis. J Leukoc Biol 1999; 65:187.
- Schrier DJ, Kunkel RG, Phan SH. The role of strain variation in murine bleomycin-induced pulmonary fibrosis. Am Rev Respir Dis 1983; 127:63.
- Hoyt DG, Lazo JS. Alterations in pulmonary mRNA encoding procollagens, fibronectin and transforming growth factor-beta precede bleomycin-induced pulmonary fibrosis in mice. J Pharmacol Exp Ther 1988; 246:765.
- Khalil N, Whitman C, Zuo L, et al. Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat. J Clin Invest 1993; 92:1812.
- Giri SN, Hyde DM, Hollinger MA. Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice. Thorax 1993; 48:959.
- Piguet PF, Vesin C, Grau GE, Thompson RC. Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. Cytokine 1993; 5:57.
- Nagase T, Uozumi N, Ishii S, et al. A pivotal role of cytosolic phospholipase A(2) in bleomycin-induced pulmonary fibrosis. Nat Med 2002; 8:480.
- Denholm EM, Phan SH. Bleomycin binding sites on alveolar macrophages. J Leukoc Biol 1990; 48:519.
- Hashimoto N, Jin H, Liu T, et al. Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest 2004; 113:243.
- Culine S, Kramar A, Théodore C, et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol 2008; 26:421.
- de Wit R, Roberts JT, Wilkinson PM, et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 2001; 19:1629.
- de Wit R, Stoter G, Kaye SB, et al. Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. J Clin Oncol 1997; 15:1837.
- Loehrer PJ Sr, Johnson D, Elson P, et al. Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. J Clin Oncol 1995; 13:470.
- Motzer RJ, Nichols CJ, Margolin KA, et al. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 2007; 25:247.
- Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998; 16:1287.
- de Wit R, Stoter G, Sleijfer DT, et al. Four cycles of BEP vs four cycles of VIP in patients with intermediate-prognosis metastatic testicular non-seminoma: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. European Organization for Research and Treatment of Cancer. Br J Cancer 1998; 78:828.
- Culine S, Theodore C, Terrier-Lacombe MJ, Droz JP. Are 3 cycles of bleomycin, etoposide and cisplatin or 4 cycles of etoposide and cisplatin equivalent optimal regimens for patients with good risk metastatic germ cell tumors of the testis? The need for a randomized trial. J Urol 1997; 157:855.
- Williams SD, Birch R, Einhorn LH, et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987; 316:1435.
- Huddart RA, Gabe R, Cafferty FH, et al. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604). Eur Urol 2015; 67:534.
- Delanoy N, Pécuchet N, Fabre E, et al. Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal Tumors: A Systematic Review and Meta-analysis. Int J Gynecol Cancer 2015; 25:1593.
- Necchi A, Miceli R, Oualla K, et al. Effect of Bleomycin Administration on the Development of Pulmonary Toxicity in Patients With Metastatic Germ Cell Tumors Receiving First-Line Chemotherapy: A Meta-Analysis of Randomized Studies. Clin Genitourin Cancer 2017; 15:213.
- Lauritsen J, Kier MG, Bandak M, et al. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin. J Clin Oncol 2016; 34:1492.
- Ranganath P, Kesler KA, Einhorn LH. Perioperative Morbidity and Mortality Associated With Bleomycin in Primary Mediastinal Nonseminomatous Germ Cell Tumor. J Clin Oncol 2016; 34:4445.
- Kesler KA, Rieger KM, Hammoud ZT, et al. A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors. Ann Thorac Surg 2008; 85:371.
- Martin WG, Ristow KM, Habermann TM, et al. Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma. J Clin Oncol 2005; 23:7614.
- Hirsch A, Vander Els N, Straus DJ, et al. Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease. J Clin Oncol 1996; 14:1297.
- Hoskin PJ, Lowry L, Horwich A, et al. Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol 2009; 27:5390.
- Jóna Á, Miltényi Z, Ujj Z, et al. Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity. Expert Opin Drug Saf 2014; 13:1291.
- Avivi I, Hardak E, Shaham B, et al. Low incidence of long-term respiratory impairment in Hodgkin lymphoma survivors. Ann Hematol 2012; 91:215.
- Böll B, Goergen H, Behringer K, et al. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood 2016; 127:2189.
- Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood 2012; 119:692.
- Stamatoullas A, Brice P, Bouabdallah R, et al. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol 2015; 170:179.
- Simpson AB, Paul J, Graham J, Kaye SB. Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours. Br J Cancer 1998; 78:1061.
- Blum RH, Carter SK, Agre K. A clinical review of bleomycin--a new antineoplastic agent. Cancer 1973; 31:903.
- Carlson RW, Sikic BI. Continuous infusion or bolus injection in cancer chemotherapy. Ann Intern Med 1983; 99:823.
- Cooper KR, Hong WK. Prospective study of the pulmonary toxicity of continuously infused bleomycin. Cancer Treat Rep 1981; 65:419.
- Kawai K, Hinotsu S, Tomobe M, Akaza H. Serum creatinine level during chemotherapy for testicular cancer as a possible predictor of bleomycin-induced pulmonary toxicity. Jpn J Clin Oncol 1998; 28:546.
- Sleijfer S, van der Mark TW, Schraffordt Koops H, Mulder NH. Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatin. Eur J Cancer 1996; 32A:550.
- Haugnes HS, Aass N, Fosså SD, et al. Pulmonary function in long-term survivors of testicular cancer. J Clin Oncol 2009; 27:2779.
- Macann A, Bredenfeld H, Müller RP, et al. Radiotherapy does not influence the severe pulmonary toxicity observed with the administration of gemcitabine and bleomycin in patients with advanced-stage Hodgkin's lymphoma treated with the BAGCOPP regimen: a report by the German Hodgkin's Lymphoma Study Group. Int J Radiat Oncol Biol Phys 2008; 70:161.
- Tryka AF, Skornik WA, Godleski JJ, Brain JD. Potentiation of bleomycin-induced lung injury by exposure to 70% oxygen. Morphologic assessment. Am Rev Respir Dis 1982; 126:1074.
- Berend N. Protective effect of hypoxia on bleomycin lung toxicity in the rat. Am Rev Respir Dis 1984; 130:307.
- Tryka AF, Godleski JJ, Brain JD. Differences in effects of immediate and delayed hyperoxia exposure on bleomycin-induced pulmonary injury. Cancer Treat Rep 1984; 68:759.
- Goldiner PL, Carlon GC, Cvitkovic E, et al. Factors influencing postoperative morbidity and mortality in patients treated with bleomycin. Br Med J 1978; 1:1664.
- Nygaard K, Smith-Erichsen N, Hatlevoll R, Refsum SB. Pulmonary complications after bleomycin, irradiation and surgery for esophageal cancer. Cancer 1978; 41:17.
- Gilson AJ, Sahn SA. Reactivation of bleomycin lung toxicity following oxygen administration. A second response to corticosteroids. Chest 1985; 88:304.
- Ingrassia TS 3rd, Ryu JH, Trastek VF, Rosenow EC 3rd. Oxygen-exacerbated bleomycin pulmonary toxicity. Mayo Clin Proc 1991; 66:173.
- Aakre BM, Efem RI, Wilson GA, et al. Postoperative acute respiratory distress syndrome in patients with previous exposure to bleomycin. Mayo Clin Proc 2014; 89:181.
- Donat SM, Levy DA. Bleomycin associated pulmonary toxicity: is perioperative oxygen restriction necessary? J Urol 1998; 160:1347.
- Chaudhary UB, Haldas JR. Long-term complications of chemotherapy for germ cell tumours. Drugs 2003; 63:1565.
- Lower EE, Strohofer S, Baughman RP. Bleomycin causes alveolar macrophages from cigarette smokers to release hydrogen peroxide. Am J Med Sci 1988; 295:193.
- Ngeow J, Tan IB, Kanesvaran R, et al. Prognostic impact of bleomycin-induced pneumonitis on the outcome of Hodgkin's lymphoma. Ann Hematol 2011; 90:67.
- Ngan HY, Liang RH, Lam WK, Chan TK. Pulmonary toxicity in patients with non-Hodgkin's lymphoma treated with bleomycin-containing combination chemotherapy. Cancer Chemother Pharmacol 1993; 32:407.
- Haas CD, Coltman CA Jr, Gottlieb JA, et al. Phase II evaluation of bleomycin. A Southwest oncology Group study. Cancer 1976; 38:8.
- Fosså SD, Kaye SB, Mead GM, et al. Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. J Clin Oncol 1998; 16:716.
- Saxman SB, Nichols CR, Einhorn LH. Pulmonary toxicity in patients with advanced-stage germ cell tumors receiving bleomycin with and without granulocyte colony stimulating factor. Chest 1997; 111:657.
- Evens AM, Cilley J, Ortiz T, et al. G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis. Br J Haematol 2007; 137:545.
- Wedgwood A, Younes A. Prophylactic use of filgrastim with ABVD and BEACOPP chemotherapy regimens for Hodgkin lymphoma. Clin Lymphoma Myeloma 2007; 8 Suppl 2:S63.
- Younes A, Fayad L, Romaguera J, et al. Safety and efficacy of once-per-cycle pegfilgrastim in support of ABVD chemotherapy in patients with Hodgkin lymphoma. Eur J Cancer 2006; 42:2976.
- Bosl GJ, Geller NL, Bajorin D, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol 1988; 6:1231.
- Grimison PS, Stockler MR, Chatfield M, et al. Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Ann Oncol 2014; 25:143.
- Comis RL, Kuppinger MS, Ginsberg SJ, et al. Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients. Cancer Res 1979; 39:5076.
- Pascual RS, Mosher MB, Sikand RS, et al. Effects of bleomycin on pulmonary function in man. Am Rev Respir Dis 1973; 108:211.
- McKeage MJ, Evans BD, Atkinson C, et al. Carbon monoxide diffusing capacity is a poor predictor of clinically significant bleomycin lung. New Zealand Clinical Oncology Group. J Clin Oncol 1990; 8:779.
- Ng AK, Li S, Neuberg D, et al. A prospective study of pulmonary function in Hodgkin's lymphoma patients. Ann Oncol 2008; 19:1754.
- Villani F, De Maria P, Bonfante V, et al. Late pulmonary toxicity after treatment for Hodgkin's disease. Anticancer Res 1997; 17:4739.
- Lewis BM, Izbicki R. Routine pulmonary function tests during bleomycin therapy. Tests may be ineffective and potentially misleading. JAMA 1980; 243:347.
- Comis RL. Detecting bleomycin pulmonary toxicity: a continued conundrum. J Clin Oncol 1990; 8:765.
- Jensen JL, Goel R, Venner PM. The effect of corticosteroid administration on bleomycin lung toxicity. Cancer 1990; 65:1291.
- Chu E, DeVita VT Jr. Bleomycin. In: Physicians' Cancere Chemotherapy Drug Manual 2016, Chu E, DeVita VT Jr. (Eds), Jones and Bartlett Learning, Burlington 2016. p.48.
- Braagalone DL.. Bleomycin. In: Drug Information Handbook for Oncology, 13th, Bragalone DL. (Ed), Lexicomp/Wolters Kluwer, Hudson OH 2016. p.212.
- Buchler T, Bomanji J, Lee SM. FDG-PET in bleomycin-induced pneumonitis following ABVD chemotherapy for Hodgkin's disease--a useful tool for monitoring pulmonary toxicity and disease activity. Haematologica 2007; 92:e120.
- von Rohr L, Klaeser B, Joerger M, et al. Increased pulmonary FDG uptake in bleomycin-associated pneumonitis. Onkologie 2007; 30:320.
- Uzel I, Ozguroglu M, Uzel B, et al. Delayed onset bleomycin-induced pneumonitis. Urology 2005; 66:195.
- White DA, Schwartzberg LS, Kris MG, Bosl GJ. Acute chest pain syndrome during bleomycin infusions. Cancer 1987; 59:1582.
- Yousem SA, Lifson JD, Colby TV. Chemotherapy-induced eosinophilic pneumonia. Relation to bleomycin. Chest 1985; 88:103.
- Sikdar T, MacVicar D, Husband JE. Pneumomediastinum complicating bleomycin related lung damage. Br J Radiol 1998; 71:1202.
- Bellamy EA, Husband JE, Blaquiere RM, Law MR. Bleomycin-related lung damage: CT evidence. Radiology 1985; 156:155.
- Silva CI, Müller NL. Drug-induced lung diseases: most common reaction patterns and corresponding high-resolution CT manifestations. Semin Ultrasound CT MR 2006; 27:111.
- Cohen MB, Austin JH, Smith-Vaniz A, et al. Nodular bleomycin toxicity. Am J Clin Pathol 1989; 92:101.
- White DA, Kris MG, Stover DE. Bronchoalveolar lavage cell populations in bleomycin lung toxicity. Thorax 1987; 42:551.
- Flieder DB, Travis WD. Pathologic characteristics of drug-induced lung disease. Clin Chest Med 2004; 25:37.
- Santrach PJ, Askin FB, Wells RJ, et al. Nodular form of bleomycin-related pulmonary injury in patients with osteogenic sarcoma. Cancer 1989; 64:806.
- Holoye PY, Luna MA, MacKay B, Bedrossian CW. Bleomycin hypersensitivity pneumonitis. Ann Intern Med 1978; 88:47.
- Hapani S, Chu D, Wu S. Eosinophilic pneumonia associated with bleomycin in a patient with mediastinal seminoma: a case report. J Med Case Rep 2010; 4:126.
- Maher J, Daly PA. Severe bleomycin lung toxicity: reversal with high dose corticosteroids. Thorax 1993; 48:92.
- White DA, Stover DE. Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids. Chest 1984; 86:723.
- Germ cell and ovarian sex cord stromal tumors
- Hodgkin lymphoma
- RISK FACTORS
- Dose and renal insufficiency
- Other chemotherapy and radiation therapy
- High fraction of inspired oxygen
- Cigarette smoking
- Colony stimulating factors
- SCREENING ASYMPTOMATIC PATIENTS FOR LUNG TOXICITY
- CLINICAL PRESENTATION
- EVALUATION OF PATIENTS WITH SUSPECTED PULMONARY TOXICITY
- Pulmonary function testing
- Bronchoalveolar lavage
- Lung biopsy
- - Pathology
- DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
- Permanent discontinuation of bleomycin
- Glucocorticoids for lung toxicity
- Supplemental oxygen and future perioperative management
- SUMMARY AND RECOMMENDATIONS