Background
In Hodgkin lymphoma (HL) the risk of developing bleomycin pulmonary toxicity (BPT) is well described. A number of factors that could potentially increase the risk of this condition have been suggested e.g. increasing age, bleomycin dose, smoking history. The use of granulocyte-colony stimulating factor (G-CSF) has also been proposed as a potential risk factor for BPT. In the present study, we have investigated the incidence of BPT in the face of possible risk factors in a cohort of HL patients treated at our institution between 1990 and 2014.
Methods
Information on clinico-pathological parameters including the occurrence of BPT, the use of filgrastim/pegfilgrastim and smoke habits was obtained from clinical records. BPT was defined as pulmonary symptoms occurring during the course of chemotherapy, presence of infiltrates on chest X-ray or CT-scan and absence of infection. Patient characteristics were correlated to the presence of BPT and use of G-CSF using the chi2-test. Overall- and progression-free survival (OS and PFS), were analyzed by the Kaplan-Meier method.
Results
413 patients with a median age of 38.5 yrs (range: 16-86 yrs) were analyzed. The M:F ratio was 1,3. A total of 155 patients (38%) had disseminated disease. B-symptoms and bulky lesions were present in 48% and 31% of the patients, respectively. A history of smoking was reported in 47% of all patients. A total of 36 patients (9%) were diagnosed with BPT. The incidence of BPT was found to be higher among patents with high stage (p<0,001) and among those presenting with B-symptoms (p=0.008), i.e. the subsets that were likely to have received the largest amounts of bleomycin. A trend was found towards a higher incidence with increasing age (p=0.06). No correlation was found between BPT and a smoking history (p=0,37). Patients presenting with BPT were more likely to have been exposed to the use of G-CSF (p=0,03). Interestingly, the highest number of BPT events was observed among the patients exposed to the PEGylated forms of G-CSF (p=0,02). When stratifying the analysis according to age, the above correlations remained significant in the age group above 45 years, but did not seem to impact the younger patients.
Conclusion
In the present study, the occurrence of BPT was correlated to the presence of disseminated disease and B-symptoms at the time of diagnosis. We also found a higher incidence of BPT among the patients that were exposed to G-CSF during the course of chemotherapy.