Department of Hematology, First Affiliated Hospital of Soochow University, Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Suzhou, China.
Department of Thrombosis and Hemostasis, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China.
Ann Hematol. 2023 Apr;102(4):777-785. doi: 10.1007/s00277-023-05106-8. Epub 2023 Feb 3.
Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.
非典型慢性髓系白血病（CML）是一种罕见的 BCR::ABL1 阴性造血干细胞疾病，其特征为粒细胞增殖和粒细胞发育不良。由于非典型 CML 的诊断具有挑战性，且其发病率较低，因此对该疾病人群进行全面的基于分子注释的分析很少，目前难以确定非典型 CML 的最佳治疗方法。为了探讨非典型 CML 的基因组景观和治疗选择，我们对 31 例非典型 CML 患者的临床数据和结局进行了系统回顾。我们观察到，非典型 CML 的分子景观高度异质，多种分子事件驱动其发病机制。非典型 CML 患者对当前疗法的反应不佳，基于低甲基化剂（HMA）的治疗的总体缓解率（ORR）为 33.3%。目前的治疗策略，包括造血干细胞移植（HSCT），并未改善非典型 CML 患者的总生存期（OS），中位生存期为 20 个月。因此，HSCT 的获益和 HSCT 的候选者仍需进一步评估。类似于急性髓系白血病（AML）的化疗后桥接异基因 HSCT 可能是适合个体的理想方案。大规模前瞻性临床研究将有助于解决这一困境。
