Infections in patients with chronic lymphocytic leukemia treated with fludarabine

Ann Intern Med. 1998 Oct 1;129(7):559-66. doi: 10.7326/0003-4819-129-7-199810010-00010.


Background: Fludarabine, a purine analogue with activity in chronic lymphocytic leukemia, is usually well tolerated. Although serious infections after fludarabine therapy have been described, a systematic analysis of the risk factors for such infections in chronic lymphocytic leukemia is lacking.

Objective: To determine the risk factors for major infection in patients with chronic lymphocytic leukemia treated with fludarabine.

Design: Retrospective review of medical records.

Setting: Cancer center.

Patients: 402 patients with chronic lymphocytic leukemia not previously treated or treated with chlorambucil (with or without prednisone) who received fludarabine (30 mg/m2 of body surface area per day for 5 days) with or without prednisone at 4-week intervals.

Results: Infections occurred more often in previously treated (144 of 248 [58%]) than in previously untreated (53 of 154 [34%]) patients (P < 0.001). Listeriosis or pneumocystosis occurred in 12 of 170 (7%) previously 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 prednisone (P = 0.003). Univariate analysis identified previous chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum beta2-microglobulin level (P < 0.001), low serum albumin level (P = 0.024), elevated serum creatinine concentration (P = 0.008), and low granulocyte count (P = 0.003) as risk factors for infection. Multivariate analysis 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 to 3.67]) as statistically significant independent risk factors for major infection. A baseline granulocyte count of more than 1000 cells/microL 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 zoster compared with 9 (6%) of 139 patients with a CD4 count greater than 50 cells/mL (P = 0.01).

Conclusions: Fludarabine used in previously treated patients with chronic lymphocytic leukemia may be associated with infections involving T-cell dysfunction, such as listeriosis, pneumocystosis, mycobacterial infections, and opportunistic fungal and viral infections. Prophylaxis or presumptive therapy should be initiated in the appropriate setting.

MeSH terms

  • Analysis of Variance
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Immunocompromised Host*
  • Immunosuppressive Agents / therapeutic use*
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Logistic Models
  • Neoplasm Staging
  • Opportunistic Infections / etiology*
  • Opportunistic Infections / prevention & control
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use


  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Immunosuppressive Agents
  • Vidarabine
  • fludarabine
  • Prednisone