title: Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy.
abstract: OBJECTIVE
  Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively.
  
  
  METHODS
  On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated.
  
  
  RESULTS
  Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy.
  
  
  CONCLUSIONS
  From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.
authors.affiliation: Institute of Hematology, University of Bari, Italy. ematba@cimedoc.uniba.it
authors.forename: V
authors.initials: V
authors.lastname: Liso
authors.forename: S
authors.initials: S
authors.lastname: Molica
authors.forename: S
authors.initials: S
authors.lastname: Capalbo
authors.forename: E
authors.initials: E
authors.lastname: Pogliani
authors.forename: C
authors.initials: C
authors.lastname: Battista
authors.forename: G
authors.initials: G
authors.lastname: Broccia
authors.forename: M
authors.initials: M
authors.lastname: Montillo
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: P
authors.initials: P
authors.lastname: Leoni
authors.forename: G
authors.initials: G
authors.lastname: Specchia
authors.forename: G
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone