PULMONARY-INSUFFICIENCY COMPLICATING THERAPY WITH HIGH-DOSE CYTOSINE-ARABINOSIDE IN 5 PEDIATRIC-PATIENTS WITH RELAPSED ACUTE MYELOGENOUS LEUKEMIA

Background. The occurrence of fatal or nearly fatal pulmonary insuffic iency in 5 of 22 pediatric patients with relapsed acute myelogenous le ukemia (AML) treated with high dose cytosine arabinoside (Ara-C) at St . Jude Children's Research Hospital, Memphis, Tennessee, and instituti ons affiliated with the Pediatric Oncology Group (FOG) is reported. Me thods. Cytosine arabinoside (1.0-1.5 g/m(2)/day) was given as a 5-day continuous infusion to all patients. Four patients with persistent leu kemia received a second 3- or 5-day course. The FOG protocol included the administration of granulocyte colony stimulating factor for the pr iming of myeloblasts. Diagnostic criteria for pulmonary insufficiency ineluded noncardiogenic pulmonary edema with exclusion of underlying c ardiorespiratory, infectious, or metabolic conditions. Autopsy materia l also was reviewed. Results. Of the 22 patients 5 died (23%), includi ng 2 who received a second course of Ara-C as a result of pulmonary in sufficiency that developed at a median of 8 days (range, 3-38 days) af ter the first course. Three patients died despite intubation and press er support. Two patients were managed successfully with colloids, diur esis, and oxygen by face mask; remission was achieved in both. The pos tmortem examination of one patient disclosed airless lungs, profound p ulmonary edema, and subpleural nodules, but no evidence of leukemia. C onclusion. Pulmonary insufficiency from high dose Ara-C varies in seve rity and may be fatal; It may occur during or after treatment. Awarene ss of this potential complication, careful attention to fluid status, and aggressive supportive care may optimize outcome.