title: Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group.
abstract: The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL), Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.
authors.affiliation: Division of Haematology I, S. Martino Hospital, Genoa, Italy. gino.santini@hsmartino.liguria.it
authors.forename: Gino
authors.initials: G
authors.lastname: Santini
authors.forename: Teodoro
authors.initials: T
authors.lastname: Chisesi
authors.forename: Sandro
authors.initials: S
authors.lastname: Nati
authors.forename: Adolfo
authors.initials: A
authors.lastname: Porcellini
authors.forename: Valerio
authors.initials: V
authors.lastname: Zoli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rizzoli
authors.forename: Simona
authors.initials: S
authors.lastname: Zupo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Marino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rubagotti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Polacco
authors.forename: Mauro
authors.initials: M
authors.lastname: Spriano
authors.forename: Renato
authors.initials: R
authors.lastname: Vimercati
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Congiu
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Ravetti
authors.forename: Savina
authors.initials: S
authors.lastname: Aversa
authors.forename: Marco
authors.initials: M
authors.lastname: Candela
authors.forename: Caterina
authors.initials: C
authors.lastname: Patti
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual / Q000188:drug therapy; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine