Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials

J Clin Oncol. 2012 Nov 10;30(32):3939-46. doi: 10.1200/JCO.2012.42.2345. Epub 2012 Oct 8.

Abstract

Purpose: 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.

Patients and 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphoma, Large-Cell, Anaplastic / drug therapy*
  • Lymphoma, Large-Cell, Anaplastic / enzymology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • beta 2-Microglobulin / blood

Substances

  • Biomarkers, Tumor
  • beta 2-Microglobulin
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases