Vadasz Brian, Zak Taylor, Aldinger Jonathan, Sukhanova Madina, Gao Juehua, Wolniak Kristy Lucile, Chen Yi-Hua, Chen Qing Ching, Ma Shuo, Tariq Hamza
Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 251 E. Huron St. 7-213F, Chicago, IL, 60611, USA.
Robert H. Lurie Comprehensive Cancer Center, Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, 675 N St Clair, Chicago, IL, 60611, USA.
Virchows Arch. 2025 Apr;486(4):739-750. doi: 10.1007/s00428-024-03920-7. Epub 2024 Sep 7.
Accelerated chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL/SLL) is a histologically aggressive subtype of CLL/SLL that lies in between conventional CLL/SLL (C-CLL/SLL) and Richter transformation (RT) on the biological spectrum. Although the histologic criteria for A-CLL/SLL were defined 14 years ago, the clinical and genetic characteristics and survival outcomes of these patients have yet to be studied in the era of novel therapies. We retrospectively analyzed the clinicopathologic, genetic, and survival characteristics of 34 patients with confirmed tissue diagnosis of A-CLL/SLL and compared them with 120 patients with C-CLL/SLL. Patients with A-CLL/SLL had significantly higher frequencies of B-symptoms, anemia and thrombocytopenia, splenomegaly, higher LDH, and more advanced Rai stages. A-CLL/SLL showed a significantly higher frequency of TP53 mutations (55.0% vs. 11.5%;p < 0.0001) and deletions (38.2% vs. 8.3%;p < 0.0001), lower isolated del(13q) (5.8% vs. 27.5%;p < 0.0001), and increased incidence of RT (11.76% vs. 0.83%;p = 0.0025). The overall survival of patients with A-CLL/SLL was significantly lower than C-CLL/SLL (median survival: 6.17 years vs. not reached; 2 and 5-year survival rates: 75.5% vs. 94.7% and 53.3% vs. 93.7%, respectively; p < 0.0001); however, novel agents have improved the outcomes dramatically compared to the previously published data in the pre-BTKi era. Our results support the categorization of A-CLL/SLL as a distinct biologically aggressive subtype of CLL/SLL and highlight the need to revise the diagnostic criteria utilizing a multifaceted approach that integrates the overall pathobiological profile of the disease, in addition to the histology.
加速期慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（A-CLL/SLL）是CLL/SLL的一种组织学上具有侵袭性的亚型，在生物学谱系上介于传统CLL/SLL（C-CLL/SLL）和Richter转化（RT）之间。尽管A-CLL/SLL的组织学标准在14年前就已确定，但在新型疗法时代，这些患者的临床、遗传特征和生存结果尚未得到研究。我们回顾性分析了34例经组织学确诊为A-CLL/SLL患者的临床病理、遗传和生存特征，并与120例C-CLL/SLL患者进行了比较。A-CLL/SLL患者出现B症状、贫血和血小板减少、脾肿大、乳酸脱氢酶升高以及Rai分期更晚的频率显著更高。A-CLL/SLL显示TP53突变（55.0%对11.5%；p＜0.0001）和缺失（38.2%对8.3%；p＜0.0001）的频率显著更高，孤立性del(13q)更低（5.8%对27.5%；p＜0.0001），RT发生率增加（11.76%对0.83%；p = 0.0025）。A-CLL/SLL患者的总生存期显著低于C-CLL/SLL（中位生存期：6.17年对未达到；2年和5年生存率分别为75.5%对94.7%和53.3%对93.7%；p＜0.0001）；然而，与BTKi时代之前发表的数据相比，新型药物显著改善了治疗结果。我们的结果支持将A-CLL/SLL归类为CLL/SLL一种独特的具有生物学侵袭性的亚型，并强调除了组织学外，还需要采用多方面方法修订诊断标准，该方法应整合疾病的整体病理生物学特征。
