mercaptopurine and Pulmonary-Fibrosis

Diffuse pulmonary diseases seen in patients receiving chemotherapy have a wide variety of etiologies including infection, involvement with the underlying disease, injury from radiation or diagnostic agents, and toxicity from chemotherapeutic drugs. In addition to concomitantly used therapeutic agents, previously administered cytotoxic drugs may enhance the toxicity of radiotherapy and vice versa. Together with the clinician, the radiologist may be able to assess the probability of drug-induced lung disease by correlating radiographic and clinical data. Useful clinical data include signs and symptoms related to the lungs, pulmonary function test results, dose and schedule of drug administration, and information concerning concomitant or previous drug or radiation therapy. Useful radiographic data include the distribution of densities seen on the chest radiograph, the presence or absence of thoracic adenopathy, and the presence or absence of pleural effusion. The diagnosis is difficult, and thus the incidence of clinical and subclinical drug-induced pneumonitis is not accurately known.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Bleomycin; Busulfan; Carmustine; Cyclophosphamide; Female; Humans; Lomustine; Lung Diseases; Lung Neoplasms; Male; Mercaptopurine; Methotrexate; Middle Aged; Pulmonary Fibrosis; Radiography

Administration of a number of cytotoxic agents has been associated with interstitial pneumonitis, alveolitis and pulmonary fibrosis. Some (bleomycin, busulfan, methotrexate) are well known to cause this problem, and others (carmustine, semustine, zinostatin, mitomycin, and chlorambucil) have only recently been recognized to do so. We review and update the available information about this form of drug toxicity. Interaction between these drugs and thoracic radiation or high oxygen fractions in inspired air has produced pneumonitis at doses lower than when the drug is used alone. Synergism between the drugs themselves when given concurrently also produces pulmonary toxicity at lower doses. With some drugs and in some patients steroids will diminish the pulmonary abnormalities, but death from hypoxia is a frequent outcome. Since early recognition of the problem and withdrawal of the injurious agent is the best treatment, physician awareness of and alertness to this toxicity and its relative risk is most important. The discovery of analogs of bleomycin with a better therapeutic index, specifically reducing pulmonary damage, is one of the goals of current cancer drug development.

Topics: Alkylating Agents; Antineoplastic Agents; Bleomycin; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Humans; Mercaptopurine; Methotrexate; Mitomycins; Nitrosourea Compounds; Procarbazine; Pulmonary Fibrosis; Zinostatin

Two cases of fatal pneumopathy during cytostatic therapy for acute lymphatic leukemia of childhood, are reported with pathoanatomical lung findings and general clinical features. Histology revealed massed atypical epithelial proliferation in the bronchiolar terminal pathways (tumourlets) with multinucleated polymorphic giant cells beside pulmonary fibrosis. As causative factors for pulmonary chages hypersensitivity reactions, direct toxicity, or pharmacologic effects are discussed. Formal pathogenesis is explained by an impairment of endothelial cells in alveolar capillaries followed by permeability disorders and interstitial edema with disturbed perfusion. Disseminated intravasal microthrombi are frequent. Restitution to integrity appears possible only under favorable conditions. If the exsudative turns into the proliferative phase, intraalveolar and interstitial pulmonary fibrosis may develop with atypical epithelial proliferations. The prognosis of cytostatics-induced pneumopathies depends essentially on the time when it is diagnosied.

Topics: Antineoplastic Agents; Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Lung; Male; Mercaptopurine; Methotrexate; Prognosis; Pulmonary Fibrosis

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.

Topics: Central Nervous System Diseases; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Pulmonary Fibrosis

Topics: Adult; Aged; Arteries; Carbon Monoxide; Cyclophosphamide; Female; Humans; Lung Compliance; Male; Mercaptopurine; Middle Aged; Oxygen; Penicillamine; Prednisone; Pulmonary Diffusing Capacity; Pulmonary Fibrosis; Respiratory Function Tests; Scleroderma, Systemic; Spirometry; Time Factors; Vital Capacity