Gong Zimu, Medeiros L Jeffrey, Cortes Jorge E, Chen Zi, Zheng Lan, Li Yan, Bai Shi, Lin Pei, Miranda Roberto N, Jorgensen Jeffrey L, McDonnell Timothy J, Wang Wei, Kantarjian Hagop M, Hu Shimin
Department of Hematopathology and.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Blood Adv. 2017 Dec 8;1(26):2541-2552. doi: 10.1182/bloodadvances.2017011858. eCollection 2017 Dec 12.
The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course of CML with HR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP.
急变期（BP）慢性髓性白血病（CML）患者的高死亡率使得识别高危（HR）患者以预防急变期的发生成为必要。在此，我们基于2326例接受酪氨酸激酶抑制剂（TKIs）治疗的CML患者队列中的额外染色体异常（ACA）谱，研究了急变期的风险。我们检查了从初始诊断到ACA出现的时间间隔（间隔1）、从ACA出现到急变期发生的时间间隔（间隔2）以及急变期发生后的生存期（间隔3）。根据与每种ACA相关的急变期风险，患者被分层为中危1组、中危2组和高危组，间隔2的中位持续时间分别为未达到、19.2个月和1.9个月。3组之间间隔1或间隔3的持续时间没有差异。包括未出现ACA的患者组成的标准风险组，这4组的5年急变期总体累积概率分别为9.8%、28.0%、41.7%和67.4%。无论细胞遗传学改变如何，发生急变期的患者在急变期前的病程相似，84.4%的急变期患者在诊断后的前5年内发生急变期。总之，间隔2是急变期风险和患者预后的主要决定因素。通过延长间隔2时长，TKI治疗可减轻与低风险ACA或无ACA相关的急变期风险，但不会改变伴有高危ACA的CML的自然病程。因此，我们识别出了一组具有急变期高危风险的患者，他们可能受益于及时的替代治疗以预防急变期的发生。
