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

H. A. Poirel, M. S. Cairo, N. A. Heerema, J. Swansbury, A. Aupérin, E. Launay, Warren G Sanger, P. Talley, S. L. Perkins, M. Raphaël, K. McCarthy, R. Sposto, M. Gerrard, A. Bernheim, C. Patte

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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.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalLeukemia
Volume23
Issue number2
DOIs
StatePublished - Jan 1 2009

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Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Chromosome Aberrations
Non-Hodgkin's Lymphoma
Disease-Free Survival
Abnormal Karyotype
Central Nervous System Diseases
Proportional Hazards Models
Cytogenetics
Bone Marrow
Pediatrics
Incidence
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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. / Poirel, H. A.; Cairo, M. S.; Heerema, N. A.; Swansbury, J.; Aupérin, A.; Launay, E.; Sanger, Warren G; Talley, P.; Perkins, S. L.; Raphaël, M.; McCarthy, K.; Sposto, R.; Gerrard, M.; Bernheim, A.; Patte, C.

In: Leukemia, Vol. 23, No. 2, 01.01.2009, p. 323-331.

Research output: Contribution to journalArticle

Poirel, HA, Cairo, MS, Heerema, NA, Swansbury, J, Aupérin, A, Launay, E, Sanger, WG, Talley, P, Perkins, SL, Raphaël, M, McCarthy, K, Sposto, R, Gerrard, M, Bernheim, A & Patte, C 2009, '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', Leukemia, vol. 23, no. 2, pp. 323-331. https://doi.org/10.1038/leu.2008.312
Poirel, H. A. ; Cairo, M. S. ; Heerema, N. A. ; Swansbury, J. ; Aupérin, A. ; Launay, E. ; Sanger, Warren G ; Talley, P. ; Perkins, S. L. ; Raphaël, M. ; McCarthy, K. ; Sposto, R. ; Gerrard, M. ; Bernheim, A. ; Patte, C. / 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. In: Leukemia. 2009 ; Vol. 23, No. 2. pp. 323-331.
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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.",
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T1 - Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma

T2 - Results of the FAB/LMB 96 international study

AU - Poirel, H. A.

AU - Cairo, M. S.

AU - Heerema, N. A.

AU - Swansbury, J.

AU - Aupérin, A.

AU - Launay, E.

AU - Sanger, Warren G

AU - Talley, P.

AU - Perkins, S. L.

AU - Raphaël, M.

AU - McCarthy, K.

AU - Sposto, R.

AU - Gerrard, M.

AU - Bernheim, A.

AU - Patte, C.

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N2 - 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.

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