Idiopathic pneumonia syndrome after high-dose chemotherapy for relapsed Hodgkin's disease

Abstract

(Goldstone et al, 1993). Rates of morbidity and mortality have improved with better supportive measures and administration of HDC at an earlier phase in the course of the disease, but procedure-related mortality remains in the region of 10-20% in most published series using autologous bone marrow transplantation (ABMT) Jones et al, 1990;Reece et al, 1991;Bierman et al, 1993). Approximately 50% of these fatalities will be as a consequence of idiopathic pneumonia syndrome (IPS). This presents with dyspnoea, pulmonary infiltrates and fever, and the differential diagnosis is between infection (often with an uncommon or unusual organism), pulmonary involvement with HD, intrapulmonary haemorrhage or druginduced pneumonitis (Clark et al, 1993). The latter is most frequently associated with high-dose BCNU (carmustine), which induces interstitial fibrosis in a dose-dependent manner. (Litam et al, 1981;Pecego et al, 1986;Weaver et al, 1993). The mechanism is poorly understood but thought to involve toxic metabolites that react with sulphydryl compounds (including glutathione) resulting in neutralization. Depletion of such compounds and inhibition of glutathione reductase in alveolar Received 19April 1995 Revised 11 October 1996 Accepted 14 October 1996 Correspondence to: D Cunningham macrophages is postulated to increase the risk of oxidant injury (Arrick et al, 1984;Clark et al, 1993).Pulmonary toxicity may occur 9 days to 12 years after starting BCNU (Durant et al, 1979) and may present with the sudden onset of dyspnoea and progress rapidly to death, or be more insidious with a fatal outcome within 2 years (Phillips et al, 1983). In a dosefinding study published in 1990 using cyclophosphamide, etoposide and BCNU (Wheeler et al, 1990) 450 mg m-2 of BCNU was the maximum tolerated dose, with a 5% mortality rate compared with 22% observed following a dose of 600 mg ni-2. Another study using the same regimen and 600 mg m-2 BCNU, published the following year, reported a 16% incidence of IPS and a 12% mortality rate (Reece et al, 1991). A more recent series (Weaver et al, 1993) reported no IPS in patients who received BCNU 300 mg m-2 a rate of 23% in patients who received 600 mg m-2.The aim of our study was to quantify the risk and time of onset of IPS at our own institution and determine the risk factors for its development and prognostic factors for outcome. PATIENTS AND METHODS Using

Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy

“…5 However, 23 out of 26 patients who developed idiopathic pneumonia syndrome following BCNU-based high-dose chemotherapy with autologous bone marrow transplantation (ABMT) for relapsed Hodgkin's disease, experienced symptoms during the first 6 months post-treatment (with the remaining three patients diagnosed between 6 and 12 months post-chemotherapy). 6 In another report, 3 26 women with breast cancer, who underwent ABMT after BCNU-based conditioning, developed pulmonary symptoms with a median onset of 10.3 weeks (range 2.4-16.6 weeks). Finally, in a retrospective study of 10 women with breast cancer and biopsy-proven pulmonary toxicity after high-dose BCNU, all became symptomatic at a mean time of 48 ± 14 days (range, 21-62 days) after the initiation of high-dose treatment.…”

Pulmonary toxicity following carmustine-based preparative regimens and autologous peripheral blood progenitor cell transplantation in hematological malignancies

“…The higher incidence of major NIPC observed in patients treated with BCV compared with those who received BEM (35% vs 12%) supports the hypothesis that CY may augment the detrimental effect of BCNU on the lungs; comparable results were observed in breast cancer patients receiving BCNU associated with CY and cisplatin. 3 In a dose toxicity study of 72 patients receiving a modified BEM regimen Ager et al 5 observed that BCNU given at the dose of 600 mg/m 2 to seven patients (five lymphomas, one ANLL, one MM), was associated with an unacceptable incidence of lung toxicity (42%); Rubio et al 4 reported idiopathic pneumonia in 28% of patients with relapsed HD receiving a BEM regimen, while in our study patients receiving BEM had minimal lung toxicity; they all had MM.…”

“…In some reports late administration of steroids may explain the high incidence of fatal NIPC. 4,5 Prophylactic use of steroids concurrent with BCNU to prevent pulmonary toxicity or progression of toxicity is still debatable: 6,7,24 its use should be tested in a randomised trial.…”

“…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][4][5][6][7][8][9][10][11][12][13] onset generally occurs within 1 year of starting BCNU. Events occurring up to 17 years later have been reported.…”

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-β1 and cyclooxygenase-2

“…3 Some risk factors, such as history of irradiation to lung, cigarette smoking, female gender and a dosage greater than 475 mg/m 2 , are known to be associated with BCNU-related pulmonary injury. 4,5 However, the pathogenetic mechanism of BCNU-associated pulmonary fibrosis has never been studied.…”