b细胞非霍奇金淋巴瘤相关噬血细胞淋巴组织细胞增多症（LA-HLH）的种系突变和患者预后

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology Pub Date : 2025-07-22 DOI:10.1016/j.seminoncol.2025.152388

Xing Zhong , Xinyu Zhu , Xiaoxia Ma , Lili Zhou , Xiu Luo , Ping Li , Yi Ding , Jianfei Fu , Jiaqi Bo , Muye Yang , Aibin Liang , Yu Zeng , Bing Xiu

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引用次数: 0

摘要

淋巴瘤相关的噬血细胞淋巴组织细胞增多症/综合征（LA-HLH/LAHS）是恶性肿瘤相关的HLH最常见的形式，并伴有异常差的预后。新出现的证据暗示种系突变是血液学异常的潜在贡献者，表明受影响个体的遗传易感性。我们对12例LA-HLH患者进行了全外显子组测序（WES），并详细分析了3例具有代表性的共存遗传疾病病例。对这些病例的临床管理策略和治疗结果进行综合评估。我们的研究发现6例（6/12）患者检测到基因突变，其中2例为体细胞突变，3例为种系突变，1例为体细胞和种系突变。在4例种系突变患者中，3例诊断为并发遗传病。大多数患者（11/12）对免疫化疗有短期反应，然后进展或复发，即使在自体造血干细胞移植（ASCT）后也是如此。有趣的是，两名患者接受了car - t细胞治疗，并取得了非常好的疗效。一名患者接受了CD19 car - t细胞输注，PFS为26个月。另一位患者接受了两次CAR-T输注，并保持完全缓解超过2年（至今）。本研究提示LA-HLH可能构成一种新的遗传淋巴瘤亚型。应该优先考虑系统的基因测序，以指导特定病例的精确治疗方法，包括免疫疗法，如car - t细胞疗法。这些见解重新定义了我们对LA-HLH发病机制和临床干预策略的理解。

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Germline mutations in B-cell non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) and patient outcomes

Lymphoma-associated hemophagocytic lymphohistiocytosis/syndrome (LA-HLH/LAHS) represents the most prevalent form of malignancy-associated HLH and is associated with an exceptionally poor prognosis. Emerging evidence implicates germline mutations as potential contributors to hematologic abnormalities, suggesting a genetic predisposition in affected individuals.

We conducted whole-exome sequencing (WES) on a cohort of 12 LA-HLH patients, with detailed analysis of 3 representative cases exhibiting coexisting genetic disorders. These cases were comprehensively evaluated for their clinical management strategies and therapeutic outcomes.

Our study revealed that gene mutations were detected in 6 patients (6/12), including 2 had somatic mutations, 3 had germline mutations, and 1 had both somatic and germline mutations. Among the 4 patients harbored germline mutations, 3 were diagnosed with concurrent genetic disease. Most patients (11/12) responded to immunochemotherapy for a short time and then progressed or relapsed, even after autologous hematopoietic stem cell transplantation (ASCT). Interestingly, two patients received CAR-T-cell therapy and achieved extremely good responses. One patient received CD19 CAR-T-cell infusion and had a PFS of 26 months. The other patient received double CAR-T infusions and has remained in complete remission for more than 2 years (until now).

This study proposes that LA-HLH may constitute a novel genetic subtype of lymphoma. Systematic genetic sequencing should be prioritized to guide precision treatment approaches in selected cases, including immunotherapies such as CAR-T-cell therapy. These insights redefine our understanding of LA-HLH pathogenesis and clinical intervention strategies.

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来源期刊

Seminars in oncology 医学-肿瘤学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

104 days

期刊介绍： Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.