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-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 [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while 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.

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B‐cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab

“…24 Even in pediatric patients with DLBCL, the presence of 8q24 rearrangements independently reduces event-free survival by 6-fold. 39 By contrast, Copie-Bergman and colleagues found that presence of MYC rearrangement did not predict shortened OS in DLBCLs treated with R-CHOP. 13 Half of our cases with MYC rearrangement also had BCL2 and/or BCL6 rearrangements.…”

Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia

“…The most commonly deleted band was 13q34 (82%). The relationship between karyotypic abnormalities and outcomes showed that + 7q and del(13q) were independently associated with a significant inferior event free survival (EFS) (hazard ratio: 2·5 (P = 0·015) and 4·0 (P = 0·0003) respectively) (Poirel et al, 2009), which agrees with prior reports suggesting a worse outcome associated with 13q abnormalities (Fig 3B, C) (Lones et al, 2004;Onciu et al, 2006). Subsequently, Nelson et al (2009) utilized FISH to show a worse overall survival in patients with any 13q deletion (Fig 4).…”

“…Additional recurrent chromosomal abnormalities have been recognized with chromosomes 1, 6, 13, 17, and 22 most commonly involved (Lones et al, 2004;Onciu et al, 2006). A large cytogenetic study performed on an international trial in children and adolescents with mature B-cell lymphoma further characterized the secondary genetic changes detectable by karyotyping (Poirel et al, 2009). The main BL-associated chromosomal aberrations were + 1q (29%), +7q (14%), and del(13q) (14%).…”

Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas

“…While the impact of additional cytogenetic abnormalities detected by conventional karyotype on clinical outcomes in Burkitt or Burkitt-like lymphomas has been the subject of several studies, [9][10][11] there is very little information regarding their diagnostic value in the classification of highgrade B-cell lymphomas. Although prompt diagnosis of Burkitt lymphoma and other high-grade B-cell lymphomas carrying MYC rearrangements is clinically important because they are aggressive and may require more intensive therapy, 12 the diagnosis sometimes can be challenging.…”