melphalan and Pulmonary-Fibrosis

The case of a patient with the diagnosis of essential thrombocythemia is presented. Following treatment with melphalan during three years the patient presented clinical and radiologic data of pulmonary fibrosis. Thoracotomy with lung biopsy histologically proving fibrosis was performed. The patient developed a true histiocytic lymphoma afterwards. The rarity of pulmonary fibrosis induced by melphalan and the exceptional association of essential thrombocythemia and histiocytic lymphoma is emphasized. The characteristics of the latter disease, diagnostic difficulties and possible treatment are commented upon.

Topics: Adult; Biopsy; Female; Humans; Lung; Lymphoma, Large B-Cell, Diffuse; Melphalan; Pulmonary Fibrosis; Thoracic Neoplasms; Thrombocythemia, Essential; Time Factors

A case of acute interstitial pneumonia with hypoxaemia is described; this occurred after the cessation of cortico steroids in a patient suffering from myeloma treated with melphalan. The absence of any microbes and the lymphocytosis in the bronchoalveolar lavage and the rapid and favourable improvement on cortico steroids led to a diagnosis of melphalan induced pneumonia. This acute form is probably due to a hypersensitivity mechanism and should be distinguished from the majority of cases of sub-acute fibrosing pneumonitis due to melphalan which have been published before. Urgent treatment with glucocorticoids is justified as well as the immediate and final cessation of the medication responsible, because it is this which will affect prognosis.

Topics: Acute Disease; Aged; Aged, 80 and over; Drug Hypersensitivity; Female; Humans; Melphalan; Pulmonary Fibrosis; Radiography

A case of fatal pulmonary fibrosis and atypical epithelial proliferation (AEP) in a patient with multiple myeloma treated with melphalan is presented. Review of 10 other autopsied patients with myeloma treated with melphalan but no thoracic radiation, other cytotoxic agents, or highdose oxygen therapy revealed one other patient who died with extensive pulmonary fibrosis and AEP. Four other patients with AEP not associated with pneumonitis or fibrosis were also found, while no such changes were found in 11 autopsy controls or 11 patients with myeloma who did not receive cytotoxic agents. Melphalan should be added to the growing list of agents capable of causing severe fibrotic pulmonary reactions.

Topics: Aged; Drug Therapy, Combination; Epithelium; Humans; Lung; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Pulmonary Fibrosis

The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2 days after exposure and a second peak dominated by macrophages 29 days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude.

Topics: Acute Disease; Animals; Chemical Warfare Agents; Disease Models, Animal; Female; Genetic Predisposition to Disease; Instillation, Drug; Intubation, Intratracheal; Killer Cells, Natural; Lymphocyte Count; Melphalan; Neutrophil Infiltration; Pneumonia; Pulmonary Fibrosis; Rats; Rats, Inbred Strains; Severity of Illness Index; Species Specificity; T-Lymphocytes, Helper-Inducer; Time Factors

Topics: Blood Urea Nitrogen; Disseminated Intravascular Coagulation; Humans; Hyperkalemia; Leukemia, Monocytic, Acute; Male; Melphalan; Middle Aged; Phosphorus; Prednisolone; Pulmonary Fibrosis; Syndrome; Uric Acid

The Authors have described a case of interstitial pneumonia due to 1-phenyl alanine (Melphalan). This case report, where a diagnosis of myeloma of the lung was excluded, was characterised by contact with a single cytotoxic agent in low doses and a short delay before the appearance of the pneumopathy. The different cytotoxic substances capable of inducing such pulmonary lesions are recalled as well as the mechanisms responsible for the phenomenon. The Authors compare their observations to the 5 well documented cases in the literature and suggest that hypersensitivity may have been a contributory factor in their case.

Topics: Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Pulmonary Fibrosis

Topics: Female; Humans; Melphalan; Middle Aged; Osteosclerosis; Pulmonary Fibrosis

We report a 59-year-old patient with chronic myeloid leukemia, who developed severe interstitial lung fibrosis after short term and sequential treatment with melphalan and busulfan. The probable additive toxicity of both agents on the pulmonary tissue is discussed.

Topics: Busulfan; Drug Synergism; Humans; Leukemia, Myeloid; Male; Melphalan; Middle Aged; Pulmonary Fibrosis

Topics: Adenocarcinoma; Aged; Breast Neoplasms; Female; Humans; Leukemia, Erythroblastic, Acute; Melphalan; Pulmonary Fibrosis; Radiotherapy; Remission, Spontaneous

Topics: Female; Humans; Lung; Male; Melphalan; Middle Aged; Pulmonary Fibrosis

Pulmonary toxicity occurs after the administration of several different chemotherapeutic agents. Pulmonary toxicity due to melphalan alone has not been documented. In the patient we describe respiratory symptoms and pulmonary infiltrates developed twice within two weeks of the second course of a monthly melphalan and prednisone regimen. Open lung biopsy revealed interstitial pneumonitis. The infiltrates cleared on both occasions when melphalan was withheld. Special studies performed seven weeks after the last dose of melphalan had been given revealed that the patient's alveolar macrophages suppressed phytohemagglutinin induced blastogenesis of his peripheral lymphocytes. Melphalan itself did not stimulate the blastogenesis of the peripheral lymphocytes. Melphalan should be added to the list of therapeutic agents that induce pulmonary disease. However, the pathogenesis of the disease remains to be elucidated.

Topics: Aged; Humans; Lung; Lymphocyte Activation; Macrophages; Male; Melphalan; Monocytes; Multiple Myeloma; Pulmonary Alveoli; Pulmonary Fibrosis; Radiography

Diffuse interstitial fibrosis developed in a patient receiving therapy with melphalan for multiple myeloma. With cessation of the administration of the alkylating agent and corticosteroid, we describe progressive radiographic improvement in this patient, accompanied by persistent severe impairment in gas exchange.

Topics: Female; Humans; Melphalan; Middle Aged; Prednisone; Pulmonary Fibrosis

Topics: Adult; Aged; Antineoplastic Agents; Busulfan; Chlorambucil; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Melphalan; Middle Aged; Multiple Myeloma; Pleural Effusion; Pulmonary Fibrosis

Topics: Antineoplastic Agents; Bleomycin; Busulfan; Humans; Male; Melphalan; Methotrexate; Middle Aged; Neoplasms; Pulmonary Fibrosis

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Melphalan; Middle Aged; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Veins; Recurrence; Vascular Diseases

A patient suffering from multiple myeloma developed pulmonary fibrosis, of a type known to be associated wtih busulphan, whilst being treated with Melphalan. The possible role of Melphalan as the causative agent is discussed. Reference is made to other possible aetiological agents and the reasons for their exclusion are discussed.

Topics: Autopsy; Bronchi; Humans; Hyperplasia; Lung; Male; Melphalan; Middle Aged; Multiple Myeloma; Pulmonary Alveoli; Pulmonary Fibrosis