title: Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy.
abstract: Abstract A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review of the biopsies of previously untreated patients in two randomized trials of rituximab without chemotherapy. In the first trial (n₁ = 53), higher WHO grades correlated with longer time to next treatment, independently of clinical prognostic factors (p = 0.030); the finding was replicated in the second trial (n₂ = 221; p = 0.019). Higher grades were associated with better treatment responses (p = 0.018). Furthermore, also grades externally confirmed by independent local pathologists correlated with time to next treatment (p = 0.048). Flow cytometry in a separate patient series showed that the intensity of CD20 increased with the malignant cell size (p < 0.00005). In conclusion, WHO grade 1 follicular lymphoma correlates with inferior outcome after rituximab monotherapy. WHO grading might provide a clinically useful tool for personalized therapy.
authors.affiliation: Department of Medicine at Huddinge, Division of Hematology, Karolinska Institutet and The Hematology Center, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Björn Engelbrekt
authors.initials: BE
authors.lastname: Wahlin
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.forename: Åsa
authors.initials: Å
authors.lastname: Jeppsson-Ahlberg
authors.forename: Eric
authors.initials: E
authors.lastname: Hjalmarsson
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Bjørn
authors.initials: B
authors.lastname: Østenstad
authors.forename: Peter D
authors.initials: PD
authors.lastname: Brown
authors.forename: Erlend Bremertun
authors.initials: EB
authors.lastname: Smeland
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D003718:Denmark; D005260:Female; D005387:Finland; D006801:Humans; D008224:Lymphoma, Follicular / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009664:Norway; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D016019:Survival Analysis; D013548:Sweden; D016896:Treatment Outcome; D014944:World Health Organization; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab