title: Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study.
abstract: OBJECTIVE
  The prognostic value of pathologic characteristics of childhood ALK-positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed.
  
  
  METHODS
  All 375 patients with systemic ALK-positive ALCL included in an international trial launched by the European Intergroup for Childhood Non-Hodgkin's Lymphoma were reviewed by an international panel of pathologists based on conventional hematoxylin and eosin-stained and immunostained sections and classified according to the 2001 WHO classification.
  
  
  RESULTS
  A small-cell (SC) or lymphohistiocytic (LH) component was observed in 114 (32%) of 361 patients, whereas ALCL of common type was diagnosed in 235 (65%) of 361 patients. Regarding the histologic subtyping of patients within the two categories of ALCL (with v without SC/LH component), the concordance between the national and international reviews was quite good, with a κ index equal to 0.67 (95% CI, 0.57 to 0.75). The presence of an SC/LH component was significantly associated with a high risk of failure (hazard ratio [HR], 2.0; 95% CI, 1.3 to 3.0; P = .002) in the multivariate analysis controlling for clinical characteristics, as well as the perivascular pattern (HR, 1.7; 95% CI, 1.1 to 2.7; P = .01), whereas CD3 positivity was significantly associated with a high risk of failure only in univariate analysis.
  
  
  CONCLUSIONS
  Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.
authors.affiliation: Cancer Research Center of Toulouse, L’Institut National de la Santé et de la Recherche Médicale U, France. laurence.lamant@inserm.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Keith
authors.initials: K
authors.lastname: McCarthy
authors.forename: Emanuele
authors.initials: E
authors.lastname: d'Amore
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Maximo
authors.initials: M
authors.lastname: Fraga
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Maldyk
authors.forename: Ingrid
authors.initials: I
authors.lastname: Simonitsch-Klupp
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Audrey
authors.initials: A
authors.lastname: Mauguen
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D002648:Child; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D010641:Phenotype; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D014178:Translocation, Genetic; D014747:Vinblastine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D014747:Vinblastine; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D008727:Methotrexate