Delayed pulmonary toxicity syndrome following high-dose chemotherapy and bone marrow transplantation for breast cancer

• Published in: American journal of respiratory and critical care medicine Vol. 157; no. 2; pp. 565 - 573
• Main Authors: WILCZYNSKI, S. W, ERASMUS, J. J, PETROS, W. P, VREDENBURGH, J. J, FOLZ, R. J
• Format: Journal Article
• Language: English
• Published: New York, NY American Lung Association 01.02.1998
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Breast Neoplasms - physiopathology; Breast Neoplasms - radiotherapy; Breast Neoplasms - therapy; Combined Modality Therapy - adverse effects; Dose-Response Relationship, Drug; Female; Humans; Infection - etiology; Lung - drug effects; Lung - physiopathology; Lung - radiation effects; Medical sciences; Middle Aged; Radiography, Thoracic; Respiratory Function Tests; Retrospective Studies; Steroids - therapeutic use; Tomography, X-Ray Computed; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Antineoplastic agent; Lung disease; Spirometry; Radiodiagnosis; Respiratory disease; Malignant tumor; Mammary gland diseases; Chemotherapy; Autograft; Polychemotherapy; Bone marrow; Interstitial pneumonitis; Delayed toxicity; Complication; Graft; Medical imagery; Adult; Female; Computerized axial tomography; Combined treatment; Mammary gland; High dose
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.157.2.9705072

We have intensely followed 45 consecutive women who underwent high-dose chemotherapy (cyclophosphamide/cisplatin/BCNU) and autologous bone marrow transplant (HDC/ABMT) for primary breast cancer with pulmonary function testing and computed tomography at regular intervals up to 126 wk (median follow-up, 72 wk). Our results show a high incidence of interstitial pneumonitis requiring steroids (64%), but no deaths due to pulmonary toxicity. The DL(CO) reaches a nadir of 58.2 +/- SEM 3.4 (expressed as a percent of baseline value) 15-18 wk following HDC/ABMT, and marginally improves with time. To a much lesser extent, vital capacity is reduced with a parallel drop in FEV1, suggesting mild restrictive changes without significant obstruction. Patients who develop pulmonary symptoms of cough or dyspnea have a corresponding significantly greater and earlier decline in DL(CO). Chest computed tomography was neither sensitive nor specific for diagnosing pulmonary toxicity. For patients who received steroids for pulmonary toxicity, there was a subsequent improvement in DL(CO) of 17.1% (p = 0.0001). Because our patients do not fit with the recent definition of idiopathic pulmonary syndrome (IPS), we propose the term delayed pulmonary toxicity syndrome (DPTS) to better describe the milder form of lung toxicity seen in our patient population. We were unable to correlate the severity of DPTS with age, tobacco use, baseline pulmonary function, or systemic exposure to BCNU, cyclophosphamide, or cisplatin. These data suggest that factor(s) other than, or in addition to, chemotherapy systemic exposure can contribute to DPTS. Furthermore, early identification and institution of systemic corticosteroids may improve lung function.