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

Abstract

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...

Clinicopathologic and Survival Characteristics of Childhood and Adolescent Non Hodgkin's Lymphoma in Yazd, Iran

“…One explanation for the relatively high incidence of extra nodal non Hodgkin lymphoma in this study (21 out of 44 cases) is increased frequency of gastrointestinal lymphomas in the Middle East. In the current study 3 year and 5 year survival were 48% and 30% respectively and median survival was 36 months which shows that there is a substantial survival difference from childhood and adolescents non Hodgkin lymphoma between Shahid Sadoughi Hospital in Yazd and many developed countries (Fukano et al, 2012;Gerrard et al, 2013;Lee et al, 2013). For example Lee et al showed that the 5-year failure-free survival, event-free survival, and overall survival rates were 86.7±2.9%, 79.1±3.5%, and 84.7±3.1%, respectively in children with non Hodgkin lymphoma (Lee et al, 2013).…”

“…In another study the estimated event-free survival at 5 years of 76.2±6.6was reported by Fukano et al, (Fukano et al, 2012). Mary Gerrard revealed that the 5-year overall survival in the 42 children and adolescents with non Hodgkin lymphoma was 73% (95%CI, 56%-84%) (Gerrard et al, 2013).…”

Pediatric MLBL: challenges remain

“…This point is clearly made by Gerrard and colleagues, who report a 5-year event-free survival (EFS) rate of 66% for stage III patients with MLBL compared with 85% for those with stage III non-MLBL DLBCL, treated with the same regimen. 1 As the authors point out, there is clearly a need to consider a new paradigm in our therapeutic approach to this disease, particularly with respect to younger patients.…”

“…Gerrard and colleagues emphasize this dilemma and note that in some cases there was insufficient tissue available for the comprehensive immunophenotyping needed to distinguish between these subtypes in their retrospective review of pathology. 1 For personal use only. on May 11, 2018. by guest www.bloodjournal.org From matter?…”

“…In the study by Gerrard and colleagues, FDG-PET was not required and results for those who may have had this imaging were not reported. 1 In the context of a research study, the effectiveness of treatment modifications based on FDG-PET findings should be investigated in future trials. Early response to therapy may also be determined through recent advances in the development of technology to measure minimal disseminated disease (MDD) and minimal residual disease (MRD).…”