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Impact of Therapy With Chlorambucil, Fludarabine, or Fludarabine Plus Chlorambucil on Infections in Patients With Chronic Lymphocytic Leukemia: Intergroup Study Cancer and Leukemia Group B 9011

From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center and Veterans Affairs Medical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle WA; The Case Western Reserve University School of Medicine, Cleveland, OH; University of Chicago Medical Center, Chicago, IL; Wayne State University School of Medicine, Detroit, MI; and National Cancer Institute of Canada Clinical Trials Group, Queens University, Kingston, Ontario, Canada.

Address reprint requests to Vicki A. Morrison, MD, Sections of Hematology/Oncology and Infectious Disease, 111E, Veterans Affairs Medical Center, One Veterans Dr, Minneapolis, MN 55417; email: morri002{at}tc.umn.edu

PURPOSE: We sought to determine whether therapy with single-agent fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL).

PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and ² tests.

RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with fludarabine plus chlorambucil had more infections than those receiving either single agent (P < .0001). Comparing the two single-agent arms, there were more infections on the fludarabine arm (P = .055) per month of follow-up. Fludarabine therapy was associated with more major infections and more herpesvirus infections compared with chlorambucil (P = .008 and P = .004, respectively). Rai stage and best response to therapy were not associated with infection. A low serum immunoglobulin G was associated with number of infections (P = .02). Age was associated with incidence of major infection in the combination arm (P = .004).

CONCLUSION: Combination therapy with fludarabine plus chlorambucil resulted in significantly more infections than treatment with either single agent. Patients receiving single-agent fludarabine had more major infections and herpesvirus infections compared with chlorambucil-treated patients.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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