title: Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.
abstract: Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.
authors.affiliation: Department of Hematology, Hospital Clinic, IDIBAPS, CIBERONC, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Magnano
authors.affiliation: Department of Hematology, Barts Cancer Institute, QMUL, London, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.affiliation: Department of Hematology, Hospital Duran y Reynals, Hospitalet de Llobregat, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: Department of Hematology, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.affiliation: Department of Hematology, ICO-Hospital Germans Trias y Pujol, Badalona, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sancho
authors.affiliation: Department of Hematology, Mutua de Terrasa, Terrasa, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Muntañola
authors.affiliation: Department of Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.affiliation: Department of Hematology, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
authors.affiliation: Department of Hematology, Hospital Joan XXIII, Tarragona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.affiliation: Department of Hematology, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Department of Hematology, Hospital Duran y Reynals, Hospitalet de Llobregat, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Domingo-Domenech
authors.affiliation: Department of Hematology, Mutua de Terrasa, Terrasa, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Estany
authors.affiliation: Department of Hematology, ICO-Hospital Germans Trias y Pujol, Badalona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Department of Hematology, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Altés
authors.affiliation: Department of Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pedro
authors.affiliation: Department of Hematology, Hospital Doctor Josep Trueta, Girona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Gardella
authors.affiliation: Department of Hematology, Hospital Sant Camil, Sant Pere de Ribas, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Asensio
authors.affiliation: Department of Hematology, Centro Médico Teknon, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Vivancos
authors.affiliation: Department of Hematology, Hospital Duran y Reynals, Hospitalet de Llobregat, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández de Sevilla
authors.affiliation: Department of Hematology, ICO-Hospital Germans Trias y Pujol, Badalona, Spain.
authors.forename: Josep María
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Hematopathology Unit, Hospital Clínic, IDIBAPS, CIBERONC, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.affiliation: Hematopathology Unit, Hospital Clínic, IDIBAPS, CIBERONC, Barcelona, Spain.
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.affiliation: Department of Hematology, Hospital Clinic, IDIBAPS, CIBERONC, Villarroel, 170, 08036, Barcelona, Spain. alopezg@clinic.ub.es.
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine
keywords: FCM regimen; Follicular lymphoma; Outcome; Safety; Secondary neoplasia