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%, P = .02), EFS (68% vs 86%, P = .02), TFS (76% vs 94%, P < .01), and OS (79% vs 94%, P = .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; P = .02). However, this prognostic impact was not statistically significant when achieving BCR-ABL <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).

克隆性染色体异常在费城染色体阴性（CCA /植^- ）中期分裂出现如慢性期患者慢性髓性白血病（CP-CML）被处理具有酪氨酸激酶抑制剂（TKI）。我们评估了598例CP-CML患者在各种TKI的临床试验中的特征和对预后的影响。CCA /植^-发生在58名患者（10％）; 最常见的是25例中的-Y（43％）和7例中的8三体性（12％）。响应于TKI治疗是为患者CCA /植类似^-和那些没有额外的染色体异常（ACAS）。我们进一步分为CCA /博士^-为那些在-Y是唯一的克隆异常，和所有其他人。我们发现患有非–Y CCA / Ph ^−的患者与没有ACA且以下5年发生率相比，无故障生存期（FFS），无事件生存期（EFS），无转化生存期（TFS）和总体生存期（OS）较差：FFS（52％vs 70％，P = .02），EFS（68％vs 86％，P = .02），TFS（76％vs 94％，P <.01）和OS（79％vs 94％，P = .03） ）。在多变量分析中，当考虑基线特征且危险比为2.81（95％置信区间为1.15-6.89；P = .02）时，非– Y CCA / Ph ⁻增加了转化或死亡的风险。然而，当达到BCR-ABL时，这种预后影响在统计学上并不显着分析中包括3个月时<10％的数据。总之，非-Y CCA /博士^-与生存下降出现在慢性期CML在不同的TKI时相关。该试验已在www.clinicaltrials.gov上注册为＃NCT00048672，＃NCT00038649和＃NCT00050531（伊马替尼）；＃NCT00254423（达沙替尼）; ＃NCT00129740（尼洛替尼）; 和NCT01570868（ponatinib）。