OPPORTUNISTIC PULMONARY INFECTIONS WITH FLUDARABINE IN PREVIOUSLY TREATED PATIENTS WITH LOW-GRADE LYMPHOID MALIGNANCIES - A ROLE FOR PNEUMOCYSTIS-CARINII PNEUMONIA PROPHYLAXIS

The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Waiter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLlt search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed, A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections, Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate, In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avivm intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P =.018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections, Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine. (C) 1995 Wiley-Liss, Inc.*