Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.
目的： 探索加速期慢性淋巴细胞白血病（aCLL）患者的临床和分子生物学特征。 方法： 回顾性分析2020年1月至2022年10月在南京医科大学第一附属医院血液科诊断的13例aCLL患者的临床资料，分析aCLL患者的临床及分子生物学特征。 结果： 13例患者诊断aCLL时的中位年龄为54（35~72）岁。5例患者既往未治疗，8例患者接受以布鲁顿酪氨酸激酶抑制剂（BTKi）为主的治疗出现疾病进展时通过病理确诊aCLL，6例存在大包块病灶（病灶最大径≥5 cm）。PET-CT显示病灶间及同一病灶内部代谢摄取存在异质性，其中代谢摄取最高处病灶的中位最大标准摄取值（SUVmax）为6.96（2.51~11.90）。免疫球蛋白重链可变区（IGHV）无突变患者占76.9%（10/13），常见的遗传学及分子学异常包括+12（42.9%，3/7）、ATM突变（50%，6/12）、NOTCH1突变（50%，6/12）。12例患者接受后续治疗，总反应率为91.7%，完全缓解率为58.3%，5例患者出现疾病进展，其中2例患者发生Richter转化，伴KRAS突变的aCLL患者无进展生存时间显著缩短（7.0个月对26.3个月，P＝0.015）。 结论： aCLL患者临床呈侵袭性，多合并预后不良因素（IGHV无突变、+12、ATM突变、NOTCH1突变等），临床怀疑疾病进展（特别是大包块病灶）且SUVmax≥5的患者在代谢摄取最高部位行活检以明确病理诊断。.
Keywords: Leukemia, lymphocytic, chronic, B-cell; Molecular biology; Positron emission tomography computed tomography; Prognosis.