The difference in the odds of development of bleomycin pulmonary toxicity in patients with germ cell tumors and Hodgkin’s lymphoma receiving granulocyte colony-stimulating factor alongside bleomycin based regimens: Systematic review and meta-analysis.

Abstract

e17015 Background: Bleomycin-induced pulmonary toxicity (BPT) is a severe adverse effect that is related to the administration of bleomycin. It increases risks of morbidity and mortality, as well as results in inferior chemotherapy outcomes. Granulocyte-colony stimulating factor (G-CSF) has been considered a possible aggravating factor for BPT. However, research that studied this association has produced mixed results. In this study, we systematically analyzed and compared the odds of developing BPT in patients with Hodgkin's lymphoma (HL) on Bleomycin Based Regimens (BBR) to patients with germ cell tumors (GCT) on BBR to test our hypothesis that the effects of BPT may vary depending on the type of cancer. Methods: A thorough literature review identified 15 studies: six concentrated on GCT, six on HL, and three that investigated both HL and GCT. The eligibility criteria for inclusion mandated that studies provide the total number of patients with HL and GCT separately, the number of patients who did and did not receive G-CSF in each disease group, and the incidence of BPT within each group. Lung findings had to be distinctly classified as BPT based on clinical or diagnostic criteria. Three studies aggregating GCT and HL as a collective entity were omitted due to the lack of independent data for the two diseases. Using the data collected, odds ratios comparing patients who received and did not receive G-CSF in each disease subset were calculated and forest plots for comprehensive analysis were generated. Results: The results of 815 patients in GCT studies and 794 patients in HL studies were analyzed. The mean age of the population in the GCT subset was 31 years, while in the HL subset, it was 35.3 years. Odds ratios were computed using data from studies that compared G-CSF and non-G-CSF groups. The results indicated no substantial difference in BPT risk between patients receiving G-CSF along with BBR and those not receiving G-CSF along with BBR among the six GCT studies (OR 1.28, 95% CI 0.84-1.95). Conversely, on analysis of the HL patient subset, significantly increased odds of acquiring BPT were noted in patients who were given G-CSF along with BBR (OR 2.07, 95% CI 1.07-4.02) when compared to those who did not receive G-CSF along with BBR. Conclusions: There is a chance that the type of cancer might be altering the incidence of BPT which could be due to the age of incidence of that cancer or due to distinct tumor microenvironments. However, a limitation of this study is the lack of information about the number of cycles each patient received. Further prospective studies are needed to understand the factors involved in BPT development so that GCT patients who need G-CSF support can receive it safely.