title: Oral fludarabine has significant activity in patients with previously untreated chronic lymphocytic leukemia, and leads to increased STAT1 levels in vivo.
abstract: Fifteen patients with previously untreated chronic lymphocytic leukemia (CLL) were treated with oral fludarabine. Toxicities were mainly hematologic, and the response rate was 80%. To assess the effect of fludarabine on the transcription factor STAT1, blood samples obtained on study entry were treated in vitro with fludarabine for 24 h, and the majority of samples displayed an expected decrease in STAT1. To determine whether similar changes occurred in vivo, we developed a flow cytometric assay to quantitate STAT1 levels. On completion of fludarabine cycle 1, CLL cells showed increased STAT1 in the majority of patients, in contrast to the in vitro findings. This may reflect a survival advantage for cells that express high levels of STAT1. In conclusion, oral fludarabine is highly active and merits further investigation in previously untreated patients with CLL. Larger studies are indicated to determine optimal timing of STAT1 assessment, and if changes in STAT1 represent an in vivo indicator of response to purine analog therapy.
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA. jonathan_friedberg@urmc.rochester.edu
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Dong
authors.forename: Sigui
authors.initials: S
authors.lastname: Li
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: Katherine
authors.initials: K
authors.lastname: Stephans
authors.forename: Kimberly
authors.initials: K
authors.lastname: Noonan
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Freedman
authors.forename: Tak
authors.initials: T
authors.lastname: Takvorian
authors.forename: Ray
authors.initials: R
authors.lastname: Jurgens
authors.forename: Traci E
authors.initials: TE
authors.lastname: Battle
authors.forename: David A
authors.initials: DA
authors.lastname: Frank
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000032:analysis / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D050794:STAT1 Transcription Factor; D016019:Survival Analysis; D015534:Trans-Activators / Q000032:analysis / Q000187:drug effects*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014740:Vidarabine; C024352:fludarabine