title: Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL).
  
  
  METHODS
  From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%.
  
  
  RESULTS
  The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed.
  
  
  CONCLUSIONS
  Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.
authors.affiliation: Cancer Research UK Medical Oncology Unit, Barts and the London, Queen Mary's School of Medicine and Dentistry, United Kingdom. silvia.montoto@cancer.org.uk.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Davies
authors.forename: Janet
authors.initials: J
authors.lastname: Matthews
authors.forename: Maria
authors.initials: M
authors.lastname: Calaminici
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Norton
authors.forename: John
authors.initials: J
authors.lastname: Amess
authors.forename: Sarah
authors.initials: S
authors.lastname: Vinnicombe
authors.forename: Rachel
authors.initials: R
authors.lastname: Waters
authors.forename: Ama Z S
authors.initials: AZ
authors.lastname: Rohatiner
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology* / Q000628:therapy; D008224:Lymphoma, Follicular / Q000473:pathology* / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*