Summary:Sixty-five patients with hematological malignancies (25 multiple myeloma, 18 Hodgkin's disease, 22 non-Hodgkin's lymphomas) who received a carmustine-based regimen followed by autologous PBPC transplantation, were studied retrospectively to evaluate the incidence of post-transplant non-infective pulmonary complications (NIPCs), risk factors predictive of NIPCs, and response to steroids. Carmustine (BCNU) given i.v. at a dose of 600 mg/m 2 was combined with etoposide and cyclophosphamide in 40 patients (BCV regimen) and with etoposide and melphalan in 25 patients (BEM regimen). Seventeen of 65 patients (26%) had one episode of NIPCs. The median time to NIPCs was 90 days (52-289). Factors that increased the risk of developing NIPCs on multivariate analysis were female sex (P Ͻ 0.001) and BCV regimen (P Ͻ 0.05). All patients with NIPCs received prednisone at a dose of 1 mg/kg body weight for 10 days then tapered by 5 mg every two days; complete response to steroids was achieved in 15 of 17 patients; one unresponsive patient died of interstitial pneumonia. BCNU given at the dose of 600 mg/m 2 is well tolerated when associated with melphalan and etoposide. In females and in patients receiving BCNU with cyclophosphamide, a BCNU dose reduction may be advisable. Bone Marrow Transplantation (2000) 25, 309-313. Keywords: carmustine; pulmonary toxicity; autologous peripheral blood progenitor cell transplantation There is evidence that several agents used in the preparative regimens for both autologous and allogeneic bone marrow transplantation may induce lung injury without evidence of infection. Agents that have been implicated include carmustine (BCNU), busulphan, cyclophosphamide (CY), and total body irradiation.1 BCNU causes toxic lung reactions characterized by chronic interstitial fibrosis, cough, dyspnea and decrease in lung diffusing capacity; toxicity related to the use of BCNU is suspected to be caused by damage to the glutathione system.2 BCNU has been included in highdose conditioning regimens for gliomas, breast cancer, Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma. Toxic pulmonary reactions have been recognized in as many as 16-64% of patients; 3-13 onset generally occurs within 1 year of starting BCNU. Events occurring up to 17 years later have been reported.14 The drug seems to cause pulmonary damage in a dose-related manner: 5,10,11 Phillips et al 6 reported a 9.5% incidence of fatal pulmonary toxicity in patients receiving BCNU doses as high as 1.200 mg/m 2 as a single agent; another report suggests no pulmonary toxicity at doses of less than 1000 mg/m 2 . 7 The threshold dose for BCNU toxicity is still controversial: lung toxicity may occur at 600 mg/m 2 when the drug is associated with other toxic agents like CY. 1,15 This report deals with patients with hematological malignancies who received a carmustine-based preparative regimen; the drug was combined with cyclophosphamide and etoposide or with etoposide and melphalan and both regimens were followed by autologous peripheral blo...
The treatment of the pulmonary toxicity induced by carmustine is nowadays based on the use of corticosteroids that generally lead to a rapid resolution of pneumonitis. On the contrary, no therapeutic alternatives are reported for those patients who do not respond to steroids. We describe a case of non-Hodgkin's lymphoma in a patient who developed a severe interstitial pneumonitis after an autologous transplantation including carmustine in the conditioning regimen. He was successfully treated with an association of steroids and cyclosporine A with a rapid improvement of symptoms and a complete resolution of pneumonitis. This is, to our knowledge, the first case of carmustine-induced pneumonitis, resistant to steroids alone, successfully treated with cyclosporine A. This suggests an immunoallergic mechanism in the pathogenesis of the damage, which can be reversed with prompt therapy.
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