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.

患有 B 细胞非霍奇金淋巴瘤 (B-NHL) 的儿童有极好的生存机会，但是，目前的临床风险分层将多达一半的患者置于接受非常强化的化学免疫治疗的高危人群中。TP53改变与许多恶性肿瘤的不良结果有关；然而，虽然在儿科 B-NHL 中很常见，但它们作为风险分类器的效用尚不清楚。我们在大型英国儿科 B-NHL 队列中评估了TP53异常（突变、缺失和/或拷贝数中性杂合性丢失）的临床意义，并确定了它们对生存的影响。TP53异常出现在 54.7% 的病例中，并且与没有TP53异常（PFS 70.0% 对 100%，p  < 0.001，OS 78.0% 对 100%，p  = 0.002）。此外，在临床定义为高风险（高 LDH 的 III 期或 IV 期）的患者中，与 TP53 异常的患者相比，没有TP53异常的患者具有更高的生存率（ PFS 100% 对 55.6%，p  = 0.005，OS 100%对比 66.7%，p  = 0.019）。在所有成对的诊断/进展伯基特淋巴瘤病例中，双等位基因TP53异常要么从表现开始维持，要么在进展时获得。TP53因此，异常定义了儿科 B-NHL 中的临床风险组，并提供了一种新的分子风险分层器，允许更个性化的治疗方案。