Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2021 Sep 1;127(17):3113-3124. doi: 10.1002/cncr.33622. Epub 2021 Apr 29.
There are limited data on the clonal mechanisms underlying leukemogenesis, prognostic factors, and optimal therapy for atypical chronic myeloid leukemia (aCML).
The authors evaluated the clinicopathologic features, outcomes, and responses to therapy of 65 patients with aCML. The median age was 67 years (range, 46-89 years).
The most frequently mutated genes included ASXL1 (83%), SRSF2 (68%), and SETBP1 (58%). Mutations in SETBP1, SRSF2, TET2, and GATA2 appeared at variant allele frequencies (VAFs) greater than 40%, whereas other RAS pathway mutations were more likely to appear at low VAFs. The acquisition of new, previously undetectable mutations at transformation was observed in 63% of the evaluable patients, with the most common involving signaling pathway mutations. Hypomethylating agents (HMAs) were associated with the highest response rates but with a short duration of response (median, 2.7 months). Therapy with ruxolitinib was not associated with clinically significant responses as a single agent or in combination with an HMA. Allogeneic stem cell transplantation was the only therapy associated with improved outcomes (hazard ratio, 0.144; 95% CI, 0.035-0.593; P = .007). Age, platelet counts, bone marrow blast percentages, and serum lactate dehydrogenase (LDH) levels were independent predictors of survival and were integrated in a multivariable model that allowed the prediction of 1- and 3-year survival.
aCML is characterized by high frequencies of ASXL1, SRSF2, and SETBP1 mutations and is associated with a high risk of acute myeloid leukemia transformation. Response and survival outcomes with current therapies remain poor. The incorporation of age, platelet counts, bone marrow blast percentages, and LDH levels can allow survival prediction, and allogeneic stem cell transplantation should be considered for all eligible patients.
关于非典型慢性髓性白血病（aCML）的白血病发生、预后因素和最佳治疗的克隆机制数据有限。
作者评估了 65 例 aCML 患者的临床病理特征、结局和治疗反应。中位年龄为 67 岁（范围为 46-89 岁）。
最常突变的基因包括 ASXL1（83%）、SRSF2（68%）和 SETBP1（58%）。SETBP1、SRSF2、TET2 和 GATA2 的突变等位基因频率（VAF）大于 40%，而其他 RAS 通路突变则更可能出现在低 VAF 中。在可评估的患者中，有 63%观察到转化时获得新的、以前未检测到的突变，最常见的涉及信号通路突变。低甲基化剂（HMAs）与最高的反应率相关，但反应持续时间短（中位数为 2.7 个月）。鲁索利替尼单药或与 HMA 联合治疗作为单一药物与临床显著反应无关。异基因造血干细胞移植是唯一与改善结局相关的治疗方法（危险比，0.144；95%置信区间，0.035-0.593；P =.007）。年龄、血小板计数、骨髓原始细胞百分比和血清乳酸脱氢酶（LDH）水平是生存的独立预测因素，并整合在一个多变量模型中，允许预测 1 年和 3 年的生存率。
aCML 的特征是 ASXL1、SRSF2 和 SETBP1 突变频率高，与急性髓性白血病转化风险高相关。目前治疗的反应和生存结局仍然较差。纳入年龄、血小板计数、骨髓原始细胞百分比和 LDH 水平可进行生存预测，所有符合条件的患者均应考虑进行异基因造血干细胞移植。
