title: [Prognostic significance of immunoglobulin variable region gene mutations in B-CLL patients treated with combination therapy fludarabine plus cyclophosphamide].
abstract: OBJECTIVE
  To study prognostic factors in previously untreated patients receiving FC regimen (fludarabine plus cyclophosphamide).
  
  
  METHODS
  We conducted a retrospective analysis of B-CLL patients observed in Hematology Research Center of Russia (Moscow) and Faculty Therapy Clinic of St. Petersburg State Medical University (St. Petersburg). All patients received FC regimen as a first line treatment (fludarabine 50 mg plus cyclophosphamide 250 mg/m2 for 3 days intravenously, repeated every 28 days).
  
  
  RESULTS
  54 patients were included into the study. The median age was 57.5 yrs (range 40-78 yrs). There were 38 males and 16 females. Before the treatment 22% patients had Binet stage A, 41%--stage B and 37%--stage C. 62% patients had unmutated subtype of B-CLL and 38% mutated subtype. 12 patients (22%) received less than 4 cycles of chemotherapy. In 8 patients (15%) there were significant delays between cycles (more than 2 months). In the whole cohort the median overall survival calculated from the time of treatment initiation was 57.4 months, the median progression free survival--24 months, and the median relapse free survival--27 moths. Mutational status of immunoglobulin variable region genes significantly influenced survival. In patients with unmutated subtype the median progression free survival was 23.6 months, while in patients with mutated subset it was not reached: 75% survival at 22.7 months (p = 0.027). Difference in progression free survival by stages (A versus B+C, A+B versus C) was not significant.
  
  
  CONCLUSIONS
  Our data show that mutational status of immunoglobulin variable region genes remains a significant prognostic factor in patients receiving combined therapy with cyclophosphamide and fludarabine.
authors.forename: E A
authors.initials: EA
authors.lastname: Nikitin
authors.forename: E A
authors.initials: EA
authors.lastname: Stadnik
authors.forename: Iu Iu
authors.initials: IuIu
authors.lastname: Lorie
authors.forename: B V
authors.initials: BV
authors.lastname: Biderman
authors.forename: N N
authors.initials: NN
authors.lastname: Tsyba
authors.forename: G N
authors.initials: GN
authors.lastname: Salogub
authors.forename: T I
authors.initials: TI
authors.lastname: Kolosheĭnova
authors.forename: L Iu
authors.initials: LIu
authors.lastname: Kolosova
authors.forename: N A
authors.initials: NA
authors.lastname: Risinskaia
authors.forename: Iu A
authors.initials: IuA
authors.lastname: Zaritskiĭ
authors.forename: L G
authors.initials: LG
authors.lastname: Kovaleva
authors.forename: A B
authors.initials: AB
authors.lastname: Sudarikov
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives