Pulmonary, Pleural, and Thoracic Changes Complicating Chemotherapy

Abstract

Chronic respiratory failure slowly developed in two pediatric patients following long-term cyclophosphamide therapy for lymphocytic malignancy. One patient survived 12 years after acute lymphocytic leukemia was diagnosed but died of respiratory failure at age 16 still in initial remission; the other, a 12-year survivor of Hodgkin disease, has progressive deterioration of pulmonary function. Each patient received cyclophosphamide (less than 70 g) during the initial years of the disease. Autopsy of the first patient and lung biopsy in the second revealed severe pulmonary fibrosis. There was loss of compliance and a dramatic change in the shape of the thorax which produced a markedly reduced anteroposterior diameter in both patients, and recurrent pneumothoraces in one.

Progressive Pulmonary Fibrosis Complicating Cyclophosphamide Therapy

“…There is no characteristic pattern of exposure, and the complication has been observed as early as one month (8) and as late as eight years (9) after initiation of cyclophosphamide treatment. In three children symptoms appeared after cessation of therapy ( 5 , 9 ) , in one case even six years later (9). The appearance of fibrosis is not related to the cumulated dose.…”

“…Pleural thickening and emphysematous changes may be seen (3). Narrowing of the AP-diameter and scoliosis due to lung shrinkage has been reported in children (9). Pulmonary function tests reveal arterial hypoxaemia, restrictive ventilatory defect, and decreased diffusion capacity.…”

“…A total dose higher than 10 g seems to be a poor prognostic feature as only one of these patients has had regression of symptoms (11). In several cases fibrosis was progressive despite corticosteroid therapy and withdrawal of cyclophosphamide (3,5,6, 9,13,14). No other therapeutic measures have been proposed.…”

Cyclophosphamide‐induced acute respiratory distress syndrome

“…Some reports were of patients with a second potential cause for interstitial pneumonitis such a second drug regime or an opportunistic infection 14–16 . The interval between the administration and the onset of respiratory symptoms is extremely variable, from a few weeks to 13 years after exposure 13,17–24 . Presentation with acute respiratory failure after just a few days of administration has also been reported 25,26 .…”

“…[14][15][16] The interval between the administration and the onset of respiratory symptoms is extremely variable, from a few weeks to 13 years after exposure. 13,[17][18][19][20][21][22][23][24] Presentation with acute respiratory failure after just a few days of administration has also been reported. 25,26 There is great variability in the doses and response to steroids among all the reports.…”