Toxicity Burden of Bleomycin Treatment in Hodgkin Lymphoma: A Systematic Literature Review

Introduction: Bleomycin has been a component of chemotherapeutic regimens for decades, typically among young individuals who may survive for long periods. Yet, toxicity from bleomycin may result in short-term and long-term health problems. The study objectives were to characterize the occurrence and severity of bleomycin toxicities and identify risk factors for bleomycin toxicity among patients with Hodgkin lymphoma.

Methods: A systematic literature review of the burden of bleomycin treatment in cancer patients was conducted using the PRISMA checklist. PubMed, EMBASE, and Cochrane Database were searched for English language articles between 1980 and March 2016 providing data on bleomycin toxicity in studies with >10 patients.

Results: Overall, 18 original research articles of good to moderate quality were included in the systematic review for patients with Hodgkin lymphoma. Pulmonary toxicity ranged from dyspnea, pulmonary fibrosis, and pneumonitis, to acute respiratory distress syndrome and respiratory tract disorders or infections. For Hodgkin lymphoma, the proportion of patients experiencing pulmonary toxicity was >5% in 12 of 17 studies, with 8 studies reporting toxicity in 13% - 28% of patients. Other studies (n=5) reported that 0% - 4.7% of patients experienced pulmonary toxicity. About 4% -5% of Hodgkin lymphoma patients had fatal pulmonary toxicity. Skin toxicity ranged from skin rash to dermatitis and erythema, with 1% - 5% of Hodgkin lymphoma patients experiencing skin toxicity after bleomycin exposure.

In the 4 studies that investigated risk factors for bleomycin-induced pulmonary toxicity among patients with Hodgkin lymphoma, low albumin level (<40 g/dL), treatment with anthracycline containing chemotherapy regimens and use of colony granulocyte stimulating factor concomitant with bleomycin were reported to be significant risk factors. No significant difference was found between patients with and without pulmonary toxicity in terms of exposure to radiation therapy, cumulative bleomycin dose, smoking history, or underlying lung involvement.

Conclusions: Long-term pulmonary toxicity was not consistently evaluated in the studies and may understate the true burden on patients. Many patients treated with bleomycin may experience toxicity and sometimes fatal toxicity. Since Hodgkin lymphoma is a highly curable malignant disease and to further improve patient outcomes, attention needs to be focused on reducing treatment-related toxicities, particularly long-term morbidity and death associated with pulmonary events.