title: High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease.
abstract: Most patients diagnosed with primary chronic cold agglutinin disease (CAD) have a clonal lymphoproliferative bone marrow disorder. Treatment with rituximab is the only well-documented effective therapy, leading to 45%-60% partial responses (PR). Complete responses (CR) are rare, and median response duration is only 11 months. In a prospective multicenter trial, 29 patients received rituximab 375 mg/m(2) on days 1, 29, 57 and 85; and fludarabine orally, 40 mg/m(2) on days 1-5, 29-34, 57-61 and 85-89. Twenty-two patients (76%) responded, 6 (21%) achieving CR and 16 (55%) PR. Among 10 patients nonresponsive to rituximab monotherapy, 1 achieved CR and 6 PR. Median increase in hemoglobin level was 3.1 g/dL among the responders and 4.0 g/dL in those who achieved CR. Lower quartile of response duration was not reached after 33 months. Estimated median response duration was more than 66 months. Grade 3-4 hematologic toxicity occurred in 12 patients (41%). In conclusion, fludarabine and rituximab combination therapy is very efficient in patients with CAD. Toxicity may be a concern, and benefits should be carefully weighed against risks in very old and comorbid patients. It remains to be established whether the combination should be first-line or an efficient second-line therapy in CAD patients requiring treatment.
authors.affiliation: Department of Medicine, Haugesund Hospital, Haugesund, Norway. sigbjorn.berentsen@haugnett.no
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Berentsen
authors.forename: Ulla
authors.initials: U
authors.lastname: Randen
authors.forename: Anne Marita
authors.initials: AM
authors.lastname: Vågan
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Anders
authors.initials: A
authors.lastname: Vik
authors.forename: Jakob
authors.initials: J
authors.lastname: Dalgaard
authors.forename: Eva-Marie
authors.initials: EM
authors.lastname: Jacobsen
authors.forename: Aud S
authors.initials: AS
authors.lastname: Thoresen
authors.forename: Klaus
authors.initials: K
authors.lastname: Beiske
authors.forename: Geir E
authors.initials: GE
authors.lastname: Tjønnfjord
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine