Abstract
Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.
Original language | English |
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Pages (from-to) | 781-789 |
Number of pages | 9 |
Journal | Leukemia |
Volume | 36 |
Issue number | 3 |
Early online date | 21 Oct 2021 |
DOIs | |
Publication status | Published - Mar 2022 |
Bibliographical note
Funding Information:This study was supported by a Blood Cancer UK Senior Bennett Fellowship (#12005), the Newcastle upon Tyne Hospitals NHS Charity, North East Promenaders Against Cancer (NEPAC), the JGW Patterson Foundation, the Little Princess Trust, the North of England Children’s Cancer Research Fund (NECCR), the Good Will Cause, the Hannah Bloom Charitable Trust, Cancer Research North East, the National Institute for Health Research (NIHR) Newcastle In Vitro Diagnostics Co-operative, the MRC/EPSRC Newcastle Molecular Pathology Node (NovoPath) and MRC Clinician Scientist Fellowship (MR/S021590/1). We thank all the patients, clinicians and staff who participated in the collection of material and clinical data at the Children’s Cancer and Leukaemia Group (CCLG) Tissue Bank. The CCLG Tissue Bank is funded by Cancer Research UK.
Publisher Copyright:
© 2021, The Author(s).
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research