E13A2 BCR-ABL 转录本会对接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的持续深度分子反应和无治疗缓解的实现产生负面影响。
The e13a2 BCR-ABL transcript negatively affects sustained deep molecular response and the achievement of treatment-free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors.
机构信息
Department of Hematology, Local Social Health Authority (ASST) Spedali Civili Brescia, Brescia, Italy.
Immunohematology and Transfusion Medicine Service, ASST Spedali Civili Brescia, Brescia, Italy.
出版信息
Cancer. 2019 May 15;125(10):1674-1682. doi: 10.1002/cncr.31977. Epub 2019 Feb 1.
BACKGROUND
Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment-free remission (TFR).
METHODS
The potential predictive role of BCR-ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors' center.
RESULTS
Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR (P = .008) and an sDMR (P = .004) was favored significantly in patients who had the e14a2 transcript. After a median of 68 months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second-generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second-generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60 months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance (P = .005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript.
CONCLUSIONS
The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.
背景
对于慢性髓性白血病（CML）患者，停止酪氨酸激酶抑制剂（TKI）治疗已成为一个现实且安全的目标。需要持续的深度分子反应（sDMR）和 TKI 停药后无分子复发才能达到持久的无治疗缓解（TFR）。
方法
在作者所在中心诊断和治疗 TKI 的严格连续、未经选择的 194 例患者中，分析 BCR-ABL 转录本在获得 sDMR 和 TFR 中的潜在预测作用。
结果
在 173 例完全可评估的患者中，67 例（38.7%）具有 e13a2 转录本，106 例（61.3%）具有 e14a2 转录本。完全细胞遗传学和主要分子缓解不受影响，而在具有 e14a2 转录本的患者中，实现 DMR（P=0.008）和 sDMR（P=0.004）的比例显著增加。中位随访 68 个月后，具有 e14a2 转录本的患者 sDMR 率为 39.6%，具有 e13a2 转录本的患者 sDMR 率为 19.4%。除转录本类型外，在多变量分析中，早期分子反应的获得和使用第二代 TKI 开始治疗均对 sDMR 的获得产生积极影响。第二代 TKI 作为一线治疗的使用增加了两种转录本类型的 sDMR 率。然而，在具有 e13a2 转录本的患者中，尽管继续治疗，但在 60 个月后获得 sDMR 的概率为 37%，并未进一步增加。在停止 TKI 治疗后获得 sDMR 的 60 例患者中的 51 例中，24 例发生分子复发，但所有患者在恢复 TKI 治疗后均恢复了分子缓解。同样，转录本类型影响 TFR 的维持（P=0.005），因为只有 2 例（3%）具有 e13a2 转录本的患者能够获得持久的 TFR，而具有 e14a2 转录本的患者中有 25 例（23.5%）能够获得持久的 TFR。
结论
在 CML 患者中，e13a2 转录本阻碍了深度反应的获得和 TKI 治疗停药的可能性。
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