title: Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials.
abstract: OBJECTIVE
  Systemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated.
  
  
  METHODS
  Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed.
  
  
  RESULTS
  Among the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.
authors.affiliation: He'matologie, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75015 Paris, France. david.sibon@nck.aphp.fr
authors.forename: David
authors.initials: D
authors.lastname: Sibon
authors.forename: Marion
authors.initials: M
authors.lastname: Fournier
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Serge
authors.initials: S
authors.lastname: Bologna
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Jean
authors.initials: J
authors.lastname: Gabarre
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Anne
authors.initials: A
authors.lastname: Sonet
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D001613:beta 2-Microglobulin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases