title: Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia: an effective but myelosuppressive regimen to be offered to patients with advanced disease.
abstract: BACKGROUND
  The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM).
  
  
  METHODS
  Forty-three patients with symptomatic WM that was untreated or pretreated with 1 line of chemotherapy received rituximab 375 mg/m(2) intravenously on day 1 and fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) intravenously on days 2 through 4. FCR was repeated every 28 days for up to 6 courses.
  
  
  RESULTS
  The overall response rate was 79%, and the major response rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good partial remissions. An amelioration of the quality of responses was observed during follow-up, leading to 18.6% of CRs. No differences in terms of responses were observed among previously treated or untreated patients. Among the clinical and laboratory features that were considered, only the β2-microglobulin level had a significant impact in terms of achieving a major response. The major toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and was the main reason for treatment discontinuation. After the end of treatment, 19 patients (44%) had long-lasting episodes of neutropenia. Three patients developed myelodysplastic syndrome during follow-up.
  
  
  CONCLUSIONS
  The FCR regimen was capable of neutralizing adverse prognostic factors and proved to be active in patients with WM, leading to rapid disease control and good-quality responses. Because myelosuppression was the main concern, further studies are warranted to optimize dosages and treatment duration.
authors: Division of Hematology, Niguarda Ca' Granda Hospital, Milan, Italy. alessandra.tedeschi@ospedaleniguarda.it
authors: Alessandra
authors: A
authors: Tedeschi
authors: Giulia
authors: G
authors: Benevolo
authors: Marzia
authors: M
authors: Varettoni
authors: Marta L
authors: ML
authors: Battista
authors: Pier L
authors: PL
authors: Zinzani
authors: Carlo
authors: C
authors: Visco
authors: Vittorio
authors: V
authors: Meneghini
authors: Pietro
authors: P
authors: Pioltelli
authors: Stefano
authors: S
authors: Sacchi
authors: Francesca
authors: F
authors: Ricci
authors: Michele
authors: M
authors: Nichelatti
authors: Francesco
authors: F
authors: Zaja
authors: Mario
authors: M
authors: Lazzarino
authors: Umbero
authors: U
authors: Vitolo
authors: Enrica
authors: E
authors: Morra
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine