附加染色体异常的费城染色体阳性慢性粒细胞白血病患者临床特征及预后分析

目的:探讨附加染色体异常的费城染色体（Ph）阳性慢性粒细胞白血病（CML）患者的临床特征及预后。方法:回顾性分析2009年1月至2019年1月于青岛大学附属医院诊断的351例Ph + CML患者资料，患者均经R显带技术进行骨髓染色体核型分析。总结初诊时附加染色体异常Ph + CML患者临床特征及核型，采用Kaplan-Meier法分析不同核型患者总生存（OS）差异。 结果:351例Ph + CML患者中，32例（9.1%）为变异易位。初诊时附加染色体异常47例，包括慢性期29例、加速期3例和急变期15例，分别占全组慢性期的9.15%（29/317）、加速期的25.00%（3/12）和急变期的68.18%（15/22），各期附加染色体异常发生率差异有统计学意义（ χ2=50.799， P<0.05）；47例附加染色体异常的Ph + CML患者中，13例为附加3种以上染色体异常的复杂核型，慢性期、加速期、急变期复杂核型比例分别为13.79%（4/29）、33.33%（1/3）、53.33%（8/15），差异有统计学意义（ χ2=9.26， P<0.05）。慢性期患者中最常见的附加染色体异常为双Ph（48.28%，14/29）、-Y（10.34%，3/29），急变期患者中最常见的为+8（26.67%，4/15）、双Ph（26.67%，4/15）。Kaplan-Meier生存分析显示，Ph + CML患者中，初诊时附加染色体异常者OS较非异常者差（ χ2=61.138， P<0.05）；初诊时附加染色体异常的Ph + CML患者中，复杂核型者OS较非复杂核型者差（ χ2=4.945， P<0.05）。 结论:附加染色体异常与CML疾病进展密切相关；附加染色体异常的Ph + CML患者的预后较只有Ph易位的患者差。附加染色体越复杂，CML急变的可能性越大，预后也越差；在CML治疗过程中出现附加染色体异常也可能导致急变的进展。

Clinical features and prognosis analysis of Philadelphia chromosome-positive chronic myeloid leukemia with additional chromosomal abnormalities

Objective:To investigate the clinical characteristics and prognosis of Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) patients with additional chromosomal abnormalities.Methods:The data of 351 CML patients with Ph-positive in the Affiliated Hospital of Qingdao University from January 2009 to January 2019 were retrospectively analyzed. The bone marrow chromosomal karyotype analysis of all patients was performed by using R-banding technique. The clinical characteristics and karyotype of Ph-positive CML patients with additional chromosomal abnormalities at initial diagnosis were summarized, and Kaplan-Meier was used to analyze the differences in overall survival (OS) of patients with different karyotypes.Results:Among 351 patients with Ph-positive CML, 32 (9.1%) cases had variant translocation. At initial diagnosis, 47 cases had additional chromosomal abnormalities including 29 cases in chronic phase accounting for 9.15% (29/317) of all patients in chronic phase, 3 cases in accelerated phase accounting for 25.00% (3/12) of all patients in accelerated phase, 15 cases in blast crisis accounting for 68.18% (15/22) of all patients in blast crisis; there was a statistically significant difference in the chromosomal abnormalities rate of all different phases ( χ2=50.799, P<0.05). Among 47 Ph-positive CML patients with additional chromosomal abnormalities, 13 patients had complex karyotypes with more than 3 additional chromosomal abnormalities, the proportion of complex karyotypes in chronic phase, accelerated phase and blast crisis was 13.79% (4/29), 33.33% (1/3) and 53.33% (8/15), respectively, and the difference was statistically significant ( χ2=9.26, P<0.05). The study showed that the most common additional chromosomal abnormalities in chronic phase were double Ph (48.28%, 14/29) and -Y (10.34%, 3/29), while the most common chromosomal abnormalities in the blast crisis were +8 (26.67%, 4/15) and double Ph (26.67%, 4/15). Kaplan-Meier survival analysis showed that at initial diagnosis the OS time of patients with additional chromosomal abnormalities was worse than that of those with the non-additional chromosomal abnormalities group ( χ2 = 61.138, P<0.05). The OS of patients with complex karyotypes for Ph - positive CML patients with additional chromosomal abnormalities at initial diagnosis was worse than that of patients with non-complex karyotypes, and the difference was significant ( χ2 = 4.945, P < 0.05). Conclusions:The additional chromosomal abnormalities is closely related to the progression of CML, and the prognosis of CML patients with additional chromosomal abnormalities is poorer than that of patients with only Ph translocation. Moreover, the more complex the additional chromosomes are, the more likely blastic changes are, and the poorer prognosis. And additional chromosomeal abnormalities during the treatment of CML patients may also lead to the progression of blastic changes.