title: The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia.
abstract: BACKGROUND
  Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment.
  
  
  METHODS
  The authors conducted a Phase II study, in which rituximab was added to fludarabine for patients with symptomatic, untreated CLL, to evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses of fludarabine (25 mg/m(2) for 5 days) followed by 4 weekly doses of rituximab (375 mg/m(2)).
  
  
  RESULTS
  On the basis of National Cancer Institute criteria, 47 of 60 patients (78%) achieved a complete remission, 9 of 60 patients (15%) achieved a partial remission, and 4 of 60 patients (7%) had no response or progressive disease. It is noteworthy that the patients experienced a long progression-free survival (PFS) from treatment (68% at 3 yrs). A significantly shorter PFS was observed in ZAP-70-positive patients (25% vs. 100% at 3 yrs; P = 0.00005), in CD38-positive patients (18% vs. 91% at 3 yrs; P = 0.0002), and in patients who had more minimal residual disease (36% vs. 77% at 2.5 yrs; P = 0.001).
  
  
  CONCLUSIONS
  With the addition of rituximab to fludarabine, improved clinical outcomes were obtained, and the stratification of patients by using ZAP-70 and CD38 may help clinicians offer more aggressive and/or experimental approaches to the treatment of patients with high-risk B-CLL subtypes.
authors.affiliation: Cattedra di Ematologia, Universitá Tor Vergata, Roma, Italy. g.delpoeta@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Maria Antonietta Irno
authors.initials: MA
authors.lastname: Consalvo
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Carla
authors.initials: C
authors.lastname: Mazzone
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Laura
authors.initials: L
authors.lastname: Gianní
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Coco
authors.forename: Maria
authors.initials: M
authors.lastname: Cantonetti
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D000069283:Rituximab; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D014740:Vidarabine; C024352:fludarabine