title: Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study.
abstract: Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.
authors.affiliation: Biological Hematological Department, CHU Avicenne-Université Paris 13, Bobigny, France. helene.antoine-poirel@uclouvain.be
authors.forename: H A
authors.initials: HA
authors.lastname: Poirel
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
authors.forename: J
authors.initials: J
authors.lastname: Swansbury
authors.forename: A
authors.initials: A
authors.lastname: Aupérin
authors.forename: E
authors.initials: E
authors.lastname: Launay
authors.forename: W G
authors.initials: WG
authors.lastname: Sanger
authors.forename: P
authors.initials: P
authors.lastname: Talley
authors.forename: S L
authors.initials: SL
authors.lastname: Perkins
authors.forename: M
authors.initials: M
authors.lastname: Raphaël
authors.forename: K
authors.initials: K
authors.lastname: McCarthy
authors.forename: R
authors.initials: R
authors.lastname: Sposto
authors.forename: M
authors.initials: M
authors.lastname: Gerrard
authors.forename: A
authors.initials: A
authors.lastname: Bernheim
authors.forename: C
authors.initials: C
authors.lastname: Patte
mesh_terms: D000293:Adolescent; D002051:Burkitt Lymphoma / Q000235:genetics / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000401:mortality; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult