Background: Little is known about lung injury caused by the agency of fludarabine therapy.

Objectives: To establish a case definition, to describe management, and to identify risk factors for fludarabine-related pulmonary toxicity.

Design: Case-control study

Setting: Tertiary-care US Army teaching hospital.

Patients: Individuals treated with fludarabine at our institution between January 1989 and June 2000

Measurements: Cases of fludarabine-related pulmonary toxicity were defined as follows: dyspnea, heat hypoxemia, and radiographic infiltrates seen in a patient treated with fludarabine; cases were exclud if there was evidence of pulmonary infection or progression of underlying lymphoproliferative disease affecting the lung For each ease, demographic data, medical history, radiographic information, available bronchoscopy and pathology data, and details of treatment were reviewed. Cases were compared with fludarabine-treated check subjects to identify potential risk factors. Comparisons were made with regard to age, form relative to sex history of underlying lung disease, lymphoproliferative diagnosis, prior chemotherapy, fludarabine treatment regimen, and pretreatment chest radiograph.

Results: During the research period, 105 patients were treated with fludarabine. The incidence of fludarabine-related pulmonary toxicity using our definition was 86% (95% confidence interval [CI], 32 to 139%) individual patient died before this entity was suspected; the remainder of the patients underwent bronchoscopy to bar infection. Patients were treated with corticosteroids with subjective and objective benefits. single patient later died of apparent infection during steroid therapy. united patient was retreated with fludarabine and symptoms of lung toxicity discloseed again. Patients (n = 9) were similar to command subjects (n = 96) with think highly of to age, gender, history of underlying lung disease, previous chemotherapy, and fludarabine regimen. Patients with chronic lymphocytic leukemia were 133 (95% CI, 16 to 3006) times more likely to have toxicity bring to maturity than patients treated with fludarabine for other diagnoses. There was a inclination toward an increased incidence in patients with interstitial infiltrates apparent upon prefludarabine chest radiographs.

Conclusions: A variety of lung conditions arise in patients treated with fludarabine; however, this agent present the appearances to cause direct pulmonary toxicity. After performing an appropriate evaluation to hinder infection, corticosteroids are an effective therapy. The relative frequent occurrence of this condition and potential for mortality underscore the ne for increased clinician awareness of fludarabine-related pulmonary toxicity and its risk factors.

solution words: chronic lymphocytic leukemia; physic toxicity; fludarabine

Abbreviations: CI = confidence interval; CLL = chronic lymphocytic leukemia; PCP = Pneumocystis carinii pneumonia

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Fludarabine monophosphate (Berlex Laboratories; Montville, NJ) is a nucleoside analog that is widely used in the treatment of low-grade lympho-proliferative malignancies including chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma. (1) As with other nucleoside analogs, fludarabine occasions bone marrow suppression and can lead to lively leukopenia. Rare cases of autoimmune hemolytic anemia have been reported. (2-4) Neurotoxicity, ranging from weakness and confusion to coma, has also been reported in patients treated with high doses of fludarabine. (5) Patients treated with fludarabine are at increased risk for opportunistic pulmonary infections. (67) Specifically, these patients are susceptible to respiratory tract infections with unusual pathogens so as Listeria monocytogenes, cytomegalovirus, respiratory syncytial virus, and Pneumocystis carinii pneumonia (PCP) (8-12) The increased incidence of PCP in patients treated with fludarabine, particularly those who have been heavily pretreated with alkylating agents, has l to recommendations for PCP prophylaxis in many instances. (13) In cases in which patients who are treated with fludarabine have symptoms exhibit that are consistent with lower respiratory tract infection, quick evaluation is indicated.

Chemotherapeutic agents as it is as bleomycin, cyclophosphamide, and methotrexate are associated with pulmonary toxicity. (14) Despite a vast experience with fludarabine, little clinical data are available regarding a possible association between this agent and lung toxicity. To date, there have been eight published reports outlining a total of 10 patients who had a syndrome disentangle consistent with possible lung toxicity secondary to fludarabine. (15-22) These are isolated case reports, and there remains no established case definition for this poorly characterized entity.

We hypothesized that pulmonary toxicity from fludarabine is a discrete entity, and we cause to growed a disease definition. We reviewed our experience with noninfectious pulmonary complications observ in patients treated with fludarabine at our institution and examined our diagnostic approach, management, and consequence in suspected cases.

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