Open AccessSpecific 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
Author(s) -
Hélène-Antoine Poirel,
Mitchell S. Cairo,
Nyla A. Heerema,
John Swansbury,
Anne Aupérin,
Erika Launay,
Warren G. Sanger,
Polly Talley,
Sherrie L. Perkins,
Martine Raphaël,
Keith McCarthy,
Richard Sposto,
Mary Gerrard,
Alain Bernheim,
Catherine Patte
Publication year - 2008
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/leu.2008.312
Subject(s) - lymphoma , hazard ratio , international prognostic index , medicine , bone marrow , diffuse large b cell lymphoma , oncology , incidence (geometry) , proportional hazards model , stage (stratigraphy) , cytogenetics , pathology , gastroenterology , biology , confidence interval , chromosome , paleontology , biochemistry , physics , gene , optics
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.