title: Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia.
abstract: We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenström macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m(2) per day for 5 days) of fludarabine and 8 infusions (375 mg/m(2) per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor response (n = 4), for overall and major response rates of 95.3% and 86.0%, respectively. Median time to progression for all patients was 51.2 months and was longer for untreated patients (P = .017) and those achieving at least a very good partial response (P = .049). Grade 3 or higher toxicities included neutropenia (n = 27), thrombocytopenia (n = 7), and pneumonia (n = 6), including 2 patients who died of non-Pneumocystis carinii pneumonia. With a median follow-up of 40.3 months, we observed 3 cases of transformation to aggressive lymphoma and 3 cases of myelodysplastic syndrome/acute myeloid leukemia. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options. This study is registered at clinicaltrials.gov as NCT00020800.
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Branagan
authors.forename: Leukothea
authors.initials: L
authors.lastname: Ioakimidis
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Soumerai
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Barry
authors.initials: B
authors.lastname: Turnbull
authors.forename: Parveen
authors.initials: P
authors.lastname: Wasi
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
authors.forename: Andrew
authors.initials: A
authors.lastname: Lister
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Matous
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000401:mortality; D009503:Neutropenia / Q000139:chemically induced / Q000401:mortality; D011014:Pneumonia / Q000139:chemically induced / Q000401:mortality; D011446:Prospective Studies; D000069283:Rituximab; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced / Q000401:mortality; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008258:Waldenstrom Macroglobulinemia / Q000178:diet therapy* / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine