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Lookup NU author(s): Dr Peixun Zhou, Dr Amir EnshaeiORCiD, Alex Newman, Dr Amy Erhorn, Amy Barnard, Dr Rachel CrosslandORCiD, Sara Wilkinson, Dr Sirintra Nakjang, Professor Anthony MoormanORCiD, Karl Wood, Dr Despoina Televantou, Dr Peter Carey, Dr Simon BomkenORCiD, Dr Christopher BaconORCiD, Professor Simon BaileyORCiD, Professor ELizabeth Molyneux, Dr Vikki Rand
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Background: Burkitt lymphoma (BL) is the most common childhood cancer in sub-Saharan Africa. Despite excellent outcomes in high-income settings, the delivery of intensive multi-agent chemo-immunotherapy is prevented in low-income countries by high costs and insufficient supportive care facilities. Consequently, patient outcome remains unsatisfactory and new therapeutic approaches are urgently needed to improve survival. Objectives: To develop a genomic risk model to stratify patients based on response to current protocols. Design/Methods: We collected 113 diagnostic samples from the Queen Elizabeth Central Hospital, Malawi (n=63) and the Children’s Cancer and Leukaemia Group (CCLG), UK (n=50). High-resolution copy number profiling data was generated using Affymetrix Oncoscan and Cytoscan arrays. Regions of copy number abnormality were identified using GISTIC2.0 and Nexus Copy Number 9.0 (BioDiscovery). The risk of relapse associated with different clinical and genomic factors was assessed using the log-rank method and Cox regression analysis. Results: Thirty focal copy number abnormalities were detected in endemic BL. Regions of gain contained known cancer-related genes, MCL1, BCL6, BACH2, MAP3K7, MDM2 and FOXO1. Comparison of the endemic and sporadic genomes identified gain of 1q, 7q and 12q to be frequent in both BL subtypes. However, differences were identified, notably 13q deletion and miR17HG gain which were significantly enriched in sporadic BL. We constructed a risk model which identified one third of endemic BL patients harbouring specific abnormalities involving 1q21.3 or 13q14.11. These patients had an increased risk of relapse (hazard ratio 4.32 (CI 95% 1.46-12.83), p=0.008). Patients within the high-risk group had a 77% risk of relapse at 12 months compared to 25% in the low-risk group (p=0.004). To investigate whether the high-risk BL patients may benefit from more intensive therapy we investigated the association between the high-risk factors and outcome of sporadic BL patients treated with more intensive protocols. Interestingly, despite differences in treatment intensity, there was no difference in outcome for endemic and sporadic patients identified as low-risk by this model. However, outcome for high-risk patients was significantly different (RR 77% versus 13%, p=0.0007 for endemic and sporadic BL respectively). Conclusion: We have developed the first risk stratification model for endemic BL which identifies patients at a high-risk of relapse who may benefit from stratified increase in treatment intensity. In contrast, low-risk patients may be candidates for treatment de-intensification to reduce toxicity-related side-effects in other healthcare settings.
Author(s): Zhou P, Enshaei A, Newman AM, Banda K, Chagaluka G, Lampert I, Van Noorden S, Erhorn A, Barnard A, Crossland RE, Wilkinson S, Nakjang S, Moorman AV, Wood K, Televantou D, Carey P, Bomken S, Bacon CM, Bailey S, Molyneux E, Rand V
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Sixth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma
Year of Conference: 2018
Pages: 40-41
Print publication date: 26/09/2018
Online publication date: 19/09/2018
Acceptance date: 19/09/2018
Date deposited: 24/04/2019
ISSN: 1365-2141
Publisher: John Wiley & Sons Ltd
URL: https://doi.org/10.1111/bjh.15536
DOI: 10.1111/bjh.15536
PubMed id: 30230525
Series Title: British Journal of Haematology
