title: Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia.
abstract: We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1-3; cyclophosphamide 200 mg/m2 IV, d 1-3; and mitoxantrone 6 mg/m2 IV, d 1, at 4-week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. 'In vitro' sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1-6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(-)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. 'In vitro' sensitivity also correlated with CR achievement (P = 0.04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment-related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(-), in patients with previously treated CLL.
authors.affiliation: Department of Haematology, Institut d'Investigacions Biomèdiques 'August Pi i Sunyer' (IDIBAPS), Hospital Clinic, Department of Haematology, Hospital de Sant Pau, Barcelona, Spain. fbosch@clinic.ub.es
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Eva
authors.initials: E
authors.lastname: Giné
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Francesc
authors.initials: F
authors.lastname: Cobo
authors.forename: María
authors.initials: M
authors.lastname: Perales
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Albert
authors.initials: A
authors.lastname: Altés
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
authors.forename: Josep M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine