INFECTIONS IN PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA TREATED WITHFLUDARABINE

Background: Fludarabine, a purine analogue with activity in chronic ly mphocytic leukemia, is usually well tolerated. Although serious infect ions after fludarabine therapy have been described, a systematic analy sis of the risk factors for such infections in chronic lymphocytic leu kemia is lacking. Objective: To determine the risk factors for major i nfection in patients with chronic lymphocytic leukemia treated with fl udarabine. Design: Retrospective review of medical records. Setting: C ancer center. Patients: 402 patients with chronic lymphocytic leukemia not previously treated or treated with chlorambucil (with or without prednisone) who received fludarabine (30 mg/m(2) of body surface area per day for 5 days) with or without prednisone at 4-week intervals. Re sults: Infections occurred more often in previously treated (144 of 24 8 [58%]) than in previously untreated (53 of 154 [34%]) patients (P < 0.001). Listeriosis or pneumocystosis occurred in 12 of 170 (7%) previ ously treated patients receiving fludarabine plus prednisone, 0 of 78 previously treated patients receiving fludarabine alone, and 2 of 154 (1%) previously untreated patients receiving fludarabine plus predniso ne (P = 0.003). Univariate analysis identified previous chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum P, microglobulin level (P < 0.001), low serum albumin level (P = 0.024), elevated serum creatinine concentration (P = 0.008), and low granuloc yte count (P = 0.003) as risk factors for infection. Multivariate anal ysis identified Rai stage III or IV (odds ratio, 1.98 [95% CI, 1.17 to 3.94]), previous treatment (odds ratio, 2.24 [CI, 1.43 to 3.51]), and elevated serum creatinine concentration (odds ratio, 1.98 [CI, 1.09 t o 3.67]) as statistically significant independent risk factors for maj or infection. A baseline granulocyte count of more than 1000 cells/mu L was protective (odds ratio, 0.54 [CI, 0.29 to 0.99]). Five (26%) of 19 patients with a CD4 count less than 50 cells/mL developed cutaneous tester compared with 9 (6%) of 139 patients with a CD4 count greater than 50 cells/mL (P = 0.01). Conclusions: Fludarabine used in previous ly treated patients with chronic lymphocytic leukemia may be associate d with infections involving T-cell dysfunction, such as listeriosis, p neumocystosis, mycobacterial infections, and opportunistic fungal and viral infections. Prophylaxis or presumptive therapy should be initiat ed in the appropriate setting.