Xu Juan, Huang Jie, Xie Liping, Liu Ting, Li Jianjun, Chen Xinchuan, Liu Zhigang, Zhao Sha, Xu Caigang, Wu Yu
Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2024 Nov 27;14:1471090. doi: 10.3389/fonc.2024.1471090. eCollection 2024.
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) characterized by its T-follicular helper (TFH) phenotype. Relapsed and refractory disease is common in AITL and often associated with a poor prognosis. The presence of epigenetic abnormalities, immune dysregulation, hyperinflammation and active angiogenesis in AITL offers potential targets for histone deacetylase (HDAC) inhibitors and immunomodulatory drugs (IMiDs). Herein, we present a case of AITL with multiple relapses over a decade. Following intensive chemotherapy and autologous stem cell transplantation (ASCT), the patient relapsed with extensive nodal and extranodal involvement, particularly pulmonary lesions, and subsequently pursued chemo-free treatments. Initially, the patient exhibited a remarkable response to single-agent chidamide, the first oral HDAC inhibitor. Soon after developing resistance to chidamide, continuous treatment with lenalidomide led to an impressive sustained complete remission lasting 64 months, followed by a diminished response for an additional 11 months. Genetic profiling of the patient revealed mutations in KMT2D and ARID1A, along with chromosomal aberrations such as del(5q). Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.
血管免疫母细胞性T细胞淋巴瘤（AITL）是外周T细胞淋巴瘤（PTCL）的一种侵袭性亚型，其特征为T滤泡辅助（TFH）表型。AITL中复发和难治性疾病很常见，且常与预后不良相关。AITL中表观遗传异常、免疫失调、过度炎症和活跃血管生成的存在为组蛋白去乙酰化酶（HDAC）抑制剂和免疫调节药物（IMiD）提供了潜在靶点。在此，我们报告一例AITL患者，其在十年间多次复发。经过强化化疗和自体干细胞移植（ASCT）后，患者复发，出现广泛的淋巴结和结外受累，尤其是肺部病变，随后接受了无化疗治疗。最初，患者对首个口服HDAC抑制剂单药西达本胺表现出显著反应。在对西达本胺产生耐药性后不久，持续使用来那度胺治疗导致持续64个月的令人印象深刻的持续完全缓解，随后又有11个月反应减弱。对该患者的基因分析显示KMT2D和ARID1A发生突变，以及诸如del(5q)等染色体畸变。值得注意的是，该病例中未出现AITL中常见的基因突变，包括RHOA、TET2、DNMT3A和IDH2。文献综述强调了AITL异质性的基因组格局以及可用治疗方案的多样性，突显了采用定制方法克服耐药性并改善这种独特淋巴瘤亚型预后的重要性。
