Recent molecular and therapeutic advances in B‐cell non‐Hodgkin lymphoma in children

Abstract

Paediatric B-cell non-Hodgkin lymphoma (B-NHL) compromises a heterogeneous group of histological entities of which Burkitt lymphoma is the most common. In resource-rich countries, the expected cure rate is in excess of 85% with application of risk-adapted short intensive chemotherapy. In recent years, large paediatric cooperative group trials have sought to improve upon outcomes by decreasing the intensity of cytotoxic treatment as well as introducing targeted therapies, such as rituximab. These efforts have resulted in excellent outcomes, however there remains a group of high-risk patients for whom novel treatment approaches are needed. In this review, we will summarize the recent paediatric clinical trials in B-NHL as well as compare treatment approaches across the major cooperative groups. We will also highlight our current understanding of the molecular biology of paediatric B-NHL with a focus on how this may help guide future rational targeted therapy.

Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma

“…Each is highly aggressive and has its own unique biology. [1][2][3][4][5] Additionally, there are rare subtypes, including pediatric-type follicular lymphoma, pediatric marginal zone lymphoma, primary central nervous system (CNS) lymphoma, and posttransplant lymphoproliferative disorder.…”

“…Sporadic Burkitt lymphoma accounts for up to 80% of pediatric B-NHL in developed nations. 3,5 Burkitt lymphoma is a germinal center mature B-NHL with a phenotype that includes expression of CD10, CD19, CD20, CD22, surface IgM in .90% of cases, and proliferation marker Ki67 in .90% of cells. Nearly all constitutively express the MYC oncogene due to translocations with the immunoglobulin heavy chain [t(8;14)(q24;q32)] in 80% of cases, or the kappa light chain [t(2;8)(p11;q24)] or lambda light chain [t(8;22)(q24;q11)] in 15% and 5%, respectively.…”

“…DLBCL accounts for 10% to 20% of pediatric B-NHL. 2,3,5 Phenotypically, DLBCLs often express light chain-restricted surface IgG as well as B-cell markers CD19, CD20, CD22, CD79a, PAX-5, and occasionally CD30, which is a nonspecific marker of activation. Expression of the proliferation marker Ki-67 is lower than in Burkitt lymphoma, usually ,90%.…”

Age‐related heterogeneity of Burkitt lymphoma: response to Mbulaiteye and Anderson

“…The prognostic difference according to the age at diagnosis of BL is still present even when combining rituximab with short‐intensive chemotherapy (Hoelzer et al , ; Minard‐Colin et al , ; Giulino‐Roth & Goldman, ). Thus, the age of the patient, and the general aging process, seems to impact BL biology.…”

Erratum

“…An error has been identified in the text of Giulino‐Roth and Goldman (), on page 533, column 1, the sentence “(KMT2A [MLL2], CREBBP/EP300 and EZH2)” should be corrected to “(KMT2D [MLL2], CREBBP/EP300 and EZH2)”…”