Repetitive high-dose therapy with cyclophosphamide, thiotepa and docetaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study.
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This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). The planned treatment was three cycles of high-dose cyclophosphamide, thiotepa and docetaxel delivered every 35 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. Eighteen patients were entered into this trial. Of the planned 54 treatment cycles, 44 were delivered and 11 patients completed all three cycles. The dose-limiting toxicities were interstitial pneumonitis and mucositis with moderately severe diarrhea (n = 3) and rash (n = 3). There were no treatment-related deaths. Of the 17 patients with evaluable disease, 16 patients responded with six patients achieving a complete remission and an additional four patients achieving no detectable disease (negative restaging including PET scan) but a persistently abnormal bone scan. At a median follow-up of 12 months, median progression-free survival was 11 months with the median overall survival not reached. The recommended doses for phase II/III studies are cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and docetaxel (100 mg/m2). (+info)
Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study.
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This prospective phase II study was undertaken to evaluate the efficacy and toxicity of early intensive therapy followed by purged autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma with high tumor burden. All patients received the VCAP regimen (vindesine, cyclophosphamide, doxorubicin and prednisone) as conventional chemotherapy and DHAP as second-line therapy. Twenty-nine consecutive patients were included in the study. Twenty-seven patients were grafted, seven in first complete remission (CR) and 20 in first partial remission (PR). Preparative therapy consisted of cyclophosphamide and total body irradiation (TBI) in all the patients. With a median follow-up of 6 years, the actuarial overall survival is 64% and the actuarial event-free survival is 55%. Two treatment-related early deaths were observed. Eleven patients were informative for serial PCR analysis of minimal residual disease after ABMT: two relapsed, four remained disease-free with PCR positivity and five were disease-free with PCR negativity. These encouraging results lay the basis of future prospective randomized trials comparing autologous stem cell transplantation as front-line treatment with conventional chemotherapy for patients with bad prognostic factors. (+info)
Interstitial pneumonia in feedlot cattle: concurrent lesions and lack of immunohistochemical evidence for bovine respiratory syncytial virus infection.
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The objectives of this study were to describe the nature and distribution of microscopic lung lesions in feedlot cattle with interstitial pneumonia and to determine whether bovine respiratory syncytial virus (BRSV) antigen was present in affected lungs. Lungs with macroscopic lesions compatible with interstitial pneumonia were collected from cattle from 5 west-central Saskatchewan feedlots that had been on feed for greater than 60 days at the time of death. Interstitial pneumonia was most consistently present in dorsal portions of caudal lung lobes and in 21/28 cases (75%) had a multifocal to coalescing distribution. All 28 lungs exhibited hyaline membrane formation and some degree of type II alveolar epithelial cell hyperplasia, consistent with an acute to subacute duration. Twenty-one of 28 cases (75%) had concurrent bronchopneumonia in at least 1 lung lobe; bronchopneumonia was grossly evident in 9/28 cases (32%). Chronic bronchitis or bronchiolitis was present in at least 1 section in 12/28 (43%) of the lungs, and 25/28 (89%) had at least 1 focus of bronchiolitis fibrosa obliterans. Bronchopneumonia and bronchiolitis fibrosa obliterans were markedly less common in 10 sets of bovine lungs obtained from an abattoir. Bovine respiratory syncytial virus antigen was demonstrated using immunohistochemistry in 2/28 cases and was associated with bronchiolar epithelial necrosis that was more severe than the bronchiolar lesions in the BRSV antigen-negative cases. Interstitial pneumonia in feedlot cattle in this study was more frequently associated with suppurative bronchopneumonia and bronchiolitis fibrosa obliterans than with BRSV infection. (+info)
Eosinophilic pneumonia-like areas in idiopathic usual interstitial pneumonia.
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Usual interstitial pneumonia is the most common idiopathic chronic interstitial pneumonia, characterized by a temporally heterogenous pattern of interstitial injury with interstitial mononuclear infiltrates, septal fibromyxoid nodules, and parenchymal scarring. This report details the presence of focal eosinophilic pneumonia in six cases of usual interstitial pneumonia in the absence of known causes of this reaction. The relationship of eosinophilic infiltrates in usual interstitial pneumonia with regard to pathogenesis, differential diagnosis, and prognosis is discussed. (+info)
Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis.
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The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II-III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc. (+info)
Pulmonary involvement in Niemann-Pick disease: case report and literature review.
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Niemann-Pick disease (NPD) is a rare, inherited, autosomal recessive, lipid storage disease. The pathognomonic intracellular accumulation of sphingomyelin results in the production and accumulation of 'foam cells'. Interstitial lung disease is a rare manifestation of NPD. We present the case of a 48-year-old white female with NPD involving the lungs, liver and spleen. The chest radiograph showed bilateral, predominantly basal reticulonodular infiltrates and serial pulmonary function tests over a period of years showed preserved expiratory airflow and a severely decreased diffusion capacity for carbon monoxide (DLCO). In view of her visceral involvement, lack of neurological symptoms and survival into adulthood, we believe our patient represents a case of type B NPD. In this type of NPD, aside from prominent hepatosplenomegaly and sexual immaturity, significant pulmonary infiltration with 'Pick cells' has been reported. To date, no therapeutic modality has been shown to alter the natural history of this disease, which results in progressive debilitation and death. This case is unique in that it provides the longest physiological follow-up in the literature, and provides data on the natural history of pulmonary involvement in NPD. (+info)
Serum KL-6 as a possible marker for amiodarone-induced pulmonary toxicity.
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Amiodarone is a useful drug for the treatment of life-threatening cardiac arrhythmias. However, amiodarone can induced pulmonary toxicity (APT) and may cause life-threatening lung damage. APT can be difficult to diagnose, but early diagnosis is important. Here, in a 51-year-old man with APT, the high serum KL-6 level was correlated with the severity of symptoms and chest X-ray findings, and it was inversely correlated with PaO2 and diffusion capacity for carbon monoxide levels. The findings suggest that the serum KL-6 level may be increased in APT and that therefore it's the determination of serum KL-6 may provide a useful indicator and/or monitoring marker of APT. KL-6 is believed to be produced and secreted by type II pneumocytes. Typical pathological findings of APT include proliferation of type II pneumocytes which may produce KL-6, and result in increased serum KL-6 levels. (+info)
MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with interstitial lung disease.
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Idiopathic inflammatory myopathies, such as polymyositis (PM), may present with general symptoms such as fever and fatigue and only minimal muscle weakness, making it difficult to make a definite diagnosis and provide adequate treatment. Here a case is described in which interstitial lung disease was the first and most prominent manifestation of PM. Later, when muscle weakness became apparent and inflammatory muscle disease was suspected the first muscle biopsy was non-diagnostic. However, magnetic resonance imaging (MRI) scans of the clinically weak thigh muscles showed high signal on T(2) weighted images, suggesting muscle inflammation more proximal to the first biopsy site. A second biopsy at this site disclosed typical histopathological findings for myositis. After treatment with prednisolone in combination with cyclophosphamide both pulmonary and muscle function improved. CONCLUSION: MRI scans of muscles may be helpful in selection of a site for muscle biopsy in patients with suspected inflammatory myopathy when a first muscle biopsy turns out to be negative. Additionally, patients with interstitial lung disease of unknown cause should be tested for muscular function to exclude an associated inflammatory muscle disorder. (+info)