title: 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.
abstract: OBJECTIVE
  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).
  
  
  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 chi(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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Hematology/Oncology and Infectious Disease, Veterans Affairs Medical Center, Minneapolis, MN 55417, USA. morri002@tc.umn.edu
authors.forename: V A
authors.initials: VA
authors.lastname: Morrison
authors.forename: K R
authors.initials: KR
authors.lastname: Rai
authors.forename: B L
authors.initials: BL
authors.lastname: Peterson
authors.forename: J E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: L
authors.initials: L
authors.lastname: Elias
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: J D
authors.initials: JD
authors.lastname: Hines
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
authors.forename: R E
authors.initials: RE
authors.lastname: Martell
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: C A
authors.initials: CA
authors.lastname: Schiffer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009864:Ontario; D012141:Respiratory Tract Infections / Q000150:complications / Q000401:mortality*; D012874:Skin Diseases, Infectious / Q000150:complications / Q000401:mortality*; D016896:Treatment Outcome; D014481:United States; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine