Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma

Abstract

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. The goal of the Children' Oncology Group NHL Committee is to identify optimal cures for every child and young adult with NHL (and LCH). Further advances will require creative solutions, including engineering study groups to combine rare populations, biology-based eligibility, alternative endpoints, facilitating international collaborations, and coordinated correlative biology.

Keywords: Langerhans cell histiocytosis; clinical trial; non-Hodgkin lymphoma; pediatric oncology.

Figure 1.. NHL and LCH Histology

[A] BURKITT (Burkitt lymphoma): The neoplastic cells are intermediate-sized and uniform with round to squared-off borders. The nuclei have one to multiple small nucleoli, and there are tingible body macrophages and abundant apoptotic cells in the background. H&E stain. Original magnification 400x. [B] DLBCL (diffuse large B-cell lymphoma): The neoplastic cells are large with a moderate amount of cytoplasm, irregular to lobulated nuclei, vesicular chromatin, and variably prominent nucleoli. H&E stain. Original magnification 400x. [C] M-PTLD/DLBCL (monomorphic post-transplant lymphoproliferative disorder with DLBCL histology): The neoplastic cells are intermediate to large with open chromatin and variably prominent nucleoli. There are small lymphocytes and occasional plasma cells in the background. H&E stain. Original magnification 400x. [D] PMBCL (primary mediastinal B-cell lymphoma): The neoplastic cells are intermediate to large with cleared out cytoplasm. There are thin bands of collagen fibrosis in the background. H&E stain. Original magnification 400x. [E] B-LBL (B-cell lymphoblastic lymphoma): The neoplastic cells are slightly larger than a normal lymphocyte and have open, pale chromatin and round to slightly irregular nuclear contours. H&E stain. Original magnification 1,000x. [F] T-LBL (T-cell lymphoblastic lymphoma): The neoplastic cells are slightly larger than a normal lymphocyte and have open, pale chromatin and irregular nuclear contours. H&E stain. Original magnification 1,000x. [G] ALCL (anaplastic large cell lymphoma): Cells are large and pleomorphic with variably prominent nucleoli. A horseshoe-shaped “hallmark” cell is present near the middle of the image. H&E stain. Original magnification 400x. [H] LCH (Langerhans cell histiocytosis): Langerhans cells show abundant cytoplasm and nuclei with folds and occasional longitudinal grooves. H&E stain.