IDIOPATHIC PNEUMONIA SYNDROME AFTER HIGH-DOSE CHEMOTHERAPY FOR RELAPSED HODGKINS-DISEASE

The risk of idiopathic pneumonia syndrome (IFS) in patients with Hodgk in's disease (HD) undergoing high-dose chemotherapy (HDC) is significa nt, and once developed IFS is potentially fatal. The aim of this study was to quantify this risk accurately and determine prognostic factors for its development and course. Using a computerized database, all pa tients with HD treated with BCNU (carmustine) containing HDC and haema topoietic support at The Royal Marsden between November 1985 and March 1994 were identified. Patient characteristics, previous treatments, d isease status at HDC, dose of BCNU, incidence and severity of IFS and survival were all determined and analysed. During the study period, 94 patients received HDC, of whom 26 (28%) had a first episode of IFS wi thin a year of HDC and 23 within 6 months. The median time to presenta tion after HDC was 93 days (range 12-336 days). The only factors that significantly increased the risk of developing IFS on multivariate ana lysis were dose of BCNU (P for trend = 0.03) and female sex (P = 0.04) . Of these 26 patients, 14 had complete resolution of all symptoms, th ree had persisting pulmonary symptoms at 6 months and the remaining ni ne died of IFS at a median of 74 days (19-418 days). All the patients who died from IFS had the first symptoms within 6 months of HDC and al l received doses of BCNU > 475 mg m(-2) (Pier trend = 0.001). For wome n receiving > 475 mg m(-2) the risk of death was significantly higher than for men (P = 0.035) but not for those receiving < 475 mg m(-2). P revious lung disease, persisting residual disease before HDC, previous bleomycin or previous mantle radiotherapy did not increase either the incidence of IFS or risk of a fatal outcome. We conclude that the mai n avoidable risk factor for fatal IFS after HDC is dose of BCNU, and t his is especially true for women. If < 475 mg m(-2) is given, even pat ients with previous mantle radiotherapy and/or previous bleomycin have a very low risk of developing fatal lung toxicity ii lung function te sts are normal.