Issa Ghayas C, Kantarjian Hagop M, Gonzalez Graciela Nogueras, Borthakur Gautam, Tang Guilin, Wierda William, Sasaki Koji, Short Nicholas J, Ravandi Farhad, Kadia Tapan, Patel Keyur, Luthra Raja, Ferrajoli Alessandra, Garcia-Manero Guillermo, Rios Mary Beth, Dellasala Sara, Jabbour Elias, Cortes Jorge E
Department of Leukemia.
Department of Biostatistics, and.
Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.
Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph occurred in 58 patients (10%); the most common were -Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph and those without additional chromosomal abnormalities (ACAs). We further categorized CCA/Ph into those in which -Y was the only clonal abnormality, and all others. We found that patients with non -Y CCA/Ph had worse failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) compared with those without ACAs with the following 5-year rates: FFS (52% vs 70%, = .02), EFS (68% vs 86%, = .02), TFS (76% vs 94%, < .01), and OS (79% vs 94%, = .03). In a multivariate analysis, non -Y CCA/Ph increased the risk of transformation or death when baseline characteristics were considered with a hazard ratio of 2.81 (95% confidence interval, 1.15-6.89; = .02). However, this prognostic impact was not statistically significant when achieving <10% at 3 months was included in the analysis. In conclusion, non -Y CCA/Ph are associated with decreased survival when emerging in patients with chronic-phase CML across various TKIs. This trial was registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, and #NCT00050531 (imatinib); #NCT00254423 (dasatinib); #NCT00129740 (nilotinib); and NCT01570868 (ponatinib).
随着慢性期慢性髓性白血病（CP-CML）患者接受酪氨酸激酶抑制剂（TKI）治疗，费城染色体阴性（CCA/Ph）中期的克隆性染色体异常逐渐显现。我们评估了598例接受各种TKI临床试验治疗的CP-CML患者的特征及预后影响。58例患者（10%）出现CCA/Ph；最常见的是25例（43%）的-Y和7例（12%）的8号染色体三体。CCA/Ph患者与无其他染色体异常（ACA）的患者对TKI治疗的反应相似。我们进一步将CCA/Ph分为仅-Y为唯一克隆性异常的患者和其他所有患者。我们发现，与无ACA的患者相比，非-Y CCA/Ph患者的无失败生存（FFS）、无事件生存（EFS）、无转化生存（TFS）和总生存（OS）更差，5年率如下：FFS（52%对70%，P = 0.02），EFS（68%对86%，P = 0.02），TFS（76%对94%，P < 0.01），OS（79%对94%，P = 0.03）。在多变量分析中，考虑基线特征时，非-Y CCA/Ph增加了转化或死亡风险，风险比为2.81（95%置信区间，1.15 - 6.89；P = 0.02）。然而，当分析中纳入3个月时达到<10%的情况时，这种预后影响无统计学意义。总之，在接受各种TKI治疗的慢性期CML患者中出现的非-Y CCA/Ph与生存降低相关。该试验在www.clinicaltrials.gov注册，注册号为#NCT00048672、#NCT00038649和#NCT00050531（伊马替尼）；#NCT00254423（达沙替尼）；#NCT00129740（尼洛替尼）；以及NCT01570868（波纳替尼）。
