Pediatric diffuse large B‐cell lymphoma demonstrates a high proliferation index, frequent c‐Myc protein expression, and a high incidence of germinal center subtype: Report of the French–American–British (FAB) international study group

Miles, Rodney R.; Raphaël, Martine; McCarthy, Keith; Wotherspoon, Andrew; Lones, Mark A.; Terrier-Lacombe, M.-J.; Patte, Catherine; Gerrard, Mary; Aupérin, Anne; Sposto, Richard; Davenport, Virginia; Cairo, Mitchell S.; Perkins, Sherrie L.

doi:10.1002/pbc.21619

Cited by 82 publications

(90 citation statements)

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“…Our data are in line with previously published immunophenotypes of pediatric DLBCL. 29 However, our data do not support a pathogenetic dichotomy between DLBCL in children and adults ("2 lymphoma model"), as initially hypothesized. For all features associated with increasing age (ABC subtype, BCL2 protein expression, absence of IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21 as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, genetic complexity), there was no clear age cut-off between pediatric and adult DLBCL.…”

Section: Discussioncontrasting

confidence: 84%

Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma

Klapper

Kreuz

Köhler

et al. 2012

Blood

167

107

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Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs. (Blood. 2012;119(8): 1882-1887)

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Section: Discussioncontrasting

confidence: 84%

Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma

Klapper

Kreuz

Köhler

et al. 2012

Blood

167

107

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“…Pediatric lymphomas differ somewhat from their adult DLBCL counterparts in that they show high expression of c-myc, low expression of bcl-2, and an increased frequency of a germinal center-like phenotype. These biological differences may bear potential therapeutic implications in pediatric lymphomas [34]. Although data on PBL in children are limited, this review did identify the occurrence of HIV-associated PBL in two young patients.…”

Section: Discussionmentioning

confidence: 99%

HIV‐associated plasmablastic lymphoma: Lessons learned from 112 published cases

2008

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Plasmablastic lymphoma (PBL) is a distinct subtype of non-Hodgkin B-cell lymphoma, originally described with a strong predilection to the oral cavity of human immunodeficiency virus (HIV)-infected individuals. Data regarding patient age and gender, HIV status, initiation of and response to highly active antiretroviral therapy (HAART), tumor extent, pathology, treatment, and outcome were extracted from 112 cases of PBL identified in the literature. The median age at presentation was 38 years with a male predominance of 7:1, and the median CD41 count was 178 cells/mm 3 . PBL presented on average 5 years after diagnosis of HIV. Common primary sites of presentation included the oral cavity, gastrointestinal tract, and lymph nodes. Most cases presented with either stage I or stage IV disease. There was a variable expression of B-cell markers in tumor cells, but plasma cell markers were expressed in all cases. EBV was detected in 74%. Chemotherapy was used to treat 55% patients and was combined with radiotherapy in 21% cases. Complete response was obtained in 66% of treated cases; the majority of these responses were seen after CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The refractory/relapsed disease rate was 54%. Death occurred in 53% of patients, with a median overall survival of 15 months. Sex, CD41 count, viral load, clinical stage, EBV status, primary site of involvement, and use of CHOP failed to show an association with survival. PBL is an aggressive B-cell lymphoma that presents in both oral and extra-oral sites of chronically HIV-infected immunosuppressed young men. Am. J. Hematol. 83:804-809, 2008. V

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“…All cases showed CD30 staining that was variable in intensity but usually weak and patchy in distribution in a predominantly cytoplasmic distribution. In the small subset of 11 cases stained for germinal center markers, 15 it was noted that 2 expressed CD10 and BCL-6, 7 expressed BCL6 without CD10 ( Figure 2B), and 2 showed only MUM-1 without CD10 or BCL-6 expression. Interestingly, all cases (11 of 11), irrespective of germinal center marker expression, showed IRF4/MUM-1 staining ( Figure 2C).…”

Section: Pathologymentioning

confidence: 98%

“…14 In addition, a subset of eleven cases had additional immunophenotypic analysis for germinal center differentiation markers CD10, BCL-6, and IRF4/MUM-1 as described previously. 15 Retrospective pathologic review of all cases was performed to confirm a diagnosis of NHL and to attempt to subclassify the lymphomas included in this analysis. The review was limited to morphology and the initial diagnostic immunophenotypic panels performed on the cases because no additional case materials were available for further workup.…”

Section: Diagnosismentioning

confidence: 99%

Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

Gerrard

Waxman

Sposto

et al. 2013

Blood

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Key Points• There are multiple histologic types of MLBCL in adolescents.• Event-free survival of MLBCL in adolescents after FAB/LMB 96 therapy is less compared to DLBCL. Mediastinal large B-cell lymphoma (MLBL) represents IntroductionMediastinal large B-cell lymphoma (MLBL) is a rare malignancy thought to arise from mature thymic B cells. Although previously considered by the World Health Organization (WHO) to be a subtype of diffuse large B-cell lymphoma (DLBCL), 1 primary mediastinal large B-cell lymphoma (PMBL) is now classified as a distinct mature B-cell neoplasm. 2 According to the Murphy staging system for childhood non-Hodgkin lymphoma (NHL), MLBL, by virtue of its primary location in the mediastinum, must be at least stage III disease even when tumor is localized above the diaphragm. 3 The Children's Cancer Group (CCG) and Berlin-FrankfurtMünster (BFM) group each reported results in children with mediastinal disease enrolled in a series of completed multicenter mature B-NHL trials, and demonstrated 5-year event-free survival (EFS) of 75% Ϯ 10% and 75% Ϯ 8%, respectively. 4,5 In contrast, a considerably higher 5-year EFS of 85% Ϯ 2% was reported for BFM patients with stage III non-primary-mediastinal B-cell NHL who received the same therapy as those with primary mediastinal disease, suggesting that MLBL may be an inherently different disease that requires alternative therapy than other identically grouped pediatric mature B-cell NHLs.With the advent of gene-expression profiling, it has become apparent that adult PMBL differs biologically from other mature B-cell NHLs, including DLBCL subtypes [1][2][3]6 and Burkitt lymphoma (BL), 7 and may in fact be a separate disease entity altogether. DNA microarrays have demonstrated similarities between PMBL and Hodgkin lymphoma (HL), suggesting that PMBL falls somewhere along the biologic spectrum between DLBCL and HL. 6,8 Recent studies have suggested that molecular hallmarks of PMBL include overexpression of genes in both the NF-B and JAK/STAT pathways (Figure 1). 9 In the present study, we report on the largest experience of pediatric patients with MLBL uniformly treated as part of the single There is an Inside Blood commentary on this article in this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Methods Study designThe FAB/LMB 96 study was an open-label, randomized cooperative international study involving 161 pediatric cancer centers in 3 national groups: the Societé Française d'Oncologie Pediatrique (SFOP: France, Belgium, and The Netherlands), Children's Oncology Group (COG; United States, Canada, and Australia), and the United Kingdom Children's Cancer Study Group (UKCCSG).It was a planned 5-year study that enrolled patients from May 1996 until June 2001. The protocol was approved by each participating center's instituti...

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Pediatric diffuse large B‐cell lymphoma demonstrates a high proliferation index, frequent c‐Myc protein expression, and a high incidence of germinal center subtype: Report of the French–American–British (FAB) international study group

Cited by 82 publications

References 39 publications

Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma

Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma

HIV‐associated plasmablastic lymphoma: Lessons learned from 112 published cases

Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

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