Respiratory Characteristics of Pulmonary Toxicity and Pneumocystis Pneumonia Associated with Bleomycin Use for Hodgkin Lymphoma

Abstract

Rationale Bleomycin is a long-standing component of the primary combination chemotherapy for Hodgkin lymphoma. Bleomycin directly injures lung epithelia, causes interstitial and hypersensitivity pneumonitis, fibrosing alveolitis, and, through immune-suppression, places recipients at risk for Pneumocystis pneumonia (PCP). While these phenomena and their risk factors are relatively well described, there is a paucity of data regarding the severity of respiratory compromise at time of diagnosis and the subsequent morbid consequences. Methods This single-center, retrospective cohort study evaluated adults who received bleomycin treatment for Hodgkin lymphoma at Mayo Clinic in Rochester, Minnesota between January 2006 and August 2018. The primary objective was to characterize the respiratory severity at time of diagnosis in those admitted to the hospital with suspected pulmonary toxicity and PCP associated with bleomycin use. Degree of oxygenation was defined by the PaO 2 :FiO 2 (PF) ratio or SaO 2 :FiO 2 (SF) ratio when an arterial blood gas was not available. Bleomycin-associated pulmonary toxicity was defined by documentation of any clinical signs or symptoms of pulmonary impairment through electronic health record review. Diagnosis of PCP was established by polymerase chain reaction. Descriptive statistics were used to summarize the data. Results Among 376 patients receiving bleomycin-containing combination therapy for Hodgkin lymphoma, 134 (34%) had suspected bleomycin pulmonary toxicity, 14 (10%) of which had concomitant PCP. Of these, 38 (28%) required admission to the hospital. The median baseline PF (N=11) and SF (N=38) ratios at the time of diagnosis were 211 (102, 267) and 429 (325, 452), respectively. Presence of concomitant PCP was not associated with worse SF (429 v. 429, p=0.72). Most (60%) had appropriate oxygen saturations (>90%) on room air at presentation, while the remainder required immediate application of nasal cannula (37%) or closed face mask (3%). Eight patients required intensive care unit admission, 6 of which required mechanical ventilation for a median 4.5 (2.1, 11) days. The median ICU and hospital lengths of stay were 3.9 (1.4, 7.4) and 3.9 (2.7, 6.7) days, respectively. Four patients died in the hospital, all of whom required mechanical ventilation, but did not have concomitant PCP. Conclusions Nearly one-third of Hodgkin lymphoma patients with bleomycin-associated pulmonary toxicity required hospital admission for a median of 3.9 days. While the majority of patients did not require aggressive respiratory support, most patients who required mechanical ventilation died in hospital. Further investigations are needed to better understand the trajectory, treatment, and long-term implications of bleomycin pulmonary toxicity in Hodgkin lymphoma patients.