Pulmonary toxicity syndrome in breast cancer patients undergoing BCNU-containing high-dose chemotherapy and autologous hematopoietic cell transplantation

We performed a retrospective review to investigate pulmonary toxicity syndr ome (PTS) in a cohort of breast cancer patients undergoing BCNU-containing high-dose chemotherapy (HDC). Our aim was to characterize presentation, ide ntify risk factors, determine outcome following therapy, and find any assoc iation with differences in survival. We reviewed the data of 152 patients w ith stage II or III or metastatic breast cancer heated with cyclophosphamid e 5625 mg/m(2) cisplatin 165 mg/m(2), and BCNU 600 mg/m(2) followed by auto logous peripheral blood hematopoietic cell transplantation. During follow-u p, PTS was diagnosed when the following criteria were met: (1) presentation with typical clinical symptoms of PTS, (2) an absolute carbon monoxide dif fusion capacity (DLCO) decline of 10% compared with pre-HDC DLCO, and (3) n o clinical evidence of active pulmonary infection. Patients were then treat ed with a course of corticosteroid therapy. The incidence of PTS for all 15 2 patients was 59%, with a median onset at 45 days (range, 21-149 days) pos t-HDC. The median absolute DLCO decrement was 26% (range, 10%-73%) at diagn osis of PTS. There was no significant correlation between patient age, stag e of breast cancer, pre-HDC chemotherapy regimen, pre-HDC chest wall radiot herapy, tobacco use, prior lung disease, or baseline pulmonary function tes t results and the development of PTS. We did observe an interesting associa tion between PTS and the development of a noncholestatic elevation of trans aminases. Of PTS patients treated with prednisone therapy for a median of 1 05.5 days (range, 44-300 days), 91% achieved resolution of their PTS withou t pulmonary sequelae. At 3 years, the overall survival (OS) of stage II or III patients who developed PTS was 84% (95% confidence interval [CI], 73%-9 5%); of metastatic breast cancer patients with PTS, the OS was 58% (95% CI, 38%-78%). These values were not significantly different from those of pati ents who did not develop PTS (91% [95% confidence interval [CI], 81%-100%] and 53% [95% CI, 32%-74%], respectively). No significant differences in dis ease-free or event-free survival were observed between patients with and wi thout PTS. The incidence of PTS in breast cancer patients heated with a BCN U-containing a HDC regimen can be remarkably high. Treatment with a course of corticosteroid therapy is successful in the vast majority.