FISH检测12号染色体三体阳性慢性淋巴细胞白血病70例临床分析

Clinical analysis of 70 chronic lymphocytic leukemia patients with trisomy 12 detected by FISH

目的总结探讨FISH检测12号染色体三体（CEP12）阳性慢性淋巴细胞白血病（CLL）患者的临床特征、治疗情况及预后。方法回顾性分析2003年5月至2015年4月接受FISH检测CEP12的330例CLL患者临床资料，比较CEP12阳性患者（70例）和CEP12阴性患者（260例）临床特征、疗效及预后差异。结果与CEP12阴性患者相比，CEP12阳性患者肝肿大（13.6%对4.0%，P=0.011）及LDH〉247 U/L（43.3%对18.5%，χ^2=15.892，P〈0.001）比例更高，而发病年龄、性别、临床分期、β2微球蛋白水平、IGHV突变比例及脾脏/淋巴结肿大等方面差异无统计学意义。CEP12阳性与阴性患者比较，FMC7阳性率更高（23.8%对12.7%，χ^2=4.730，P=0.030），CD23阳性率更低（95.2%对99.6%，P=0.033）。氟达拉滨组、利妥昔单抗组、传统治疗组总有效率（ORR）分别为77.5%（31/40）、84.8%（56/66）、45.4%（50/110），差异有统计学意义，且传统治疗组ORR均低于氟达拉滨组及利妥昔单抗组；氟达拉滨组中CEP12阳性患者ORR低于CEP12阴性患者（42.9%对84.8%，P=0.034）；而利妥昔单抗组中CEP12阳性患者ORR高于CEP12阴性患者（91.7%对81.0%），但差异无统计学意义（P=0.306）。CEP12阳性患者中位诊断至起始治疗时间为22.6（95%CI 15.4-31.7）个月，中位总生存（OS）时间为118.5（95%CI 74.5-162.4）个月，5年无进展生存（PFS）及OS率分别为（52.9±7.6）%、（74.8±6.6）%。CEP12阳性与阴性患者比较，PFS（χ^2=0.410，P=0.478）及OS（χ^2=0.052，P=0.180）差异均无统计学意义。结论CEP12阳性CLL患者临床肝肿大及LDH增高更为常见，传统治疗疗效最差，单用氟达拉滨疗效不如CEP12阴性患者，但予含利妥昔单抗的治疗方案其疗效与CEP12阴性患者相当。

ObjectiveTo summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia （CLL） patients with trisomy 12 by using FISH （CEP12）.MethodsClinical data of 330 CLL patients were analyzed retrospectively by using FISH （CEP12） to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients （70 cases） were compared with those CEP12 negative patients （260 cases）.ObjectiveTo summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia （CLL） patients with trisomy 12 by using FISH （CEP12）.MethodsClinical data of 330 CLL patients were analyzed retrospectively by using FISH （CEP12） to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients （70 cases） were compared with those CEP12 negative patients （260 cases）.ResultsCompared with CEP12 negative CLL patients, the proportion of hepatomegaly （13.6% vs 4.0%, P=0.011） and LDH〉247 U/L （43.3% vs 18.5%, χ^2=15.892, P〈0.001） in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β2-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 （23.8% vs 12.7%, χ^2=4.730, P=0.030）, and lower ratio of CD23 （95.2% vs 99.6%, P=0.033）. The overall response rates （ORR） in Fludarabine （without Rituximab）, Rituximab （with or without Fludarabine） and the traditional chemotherapy group （chlorambucil, CHOP or CHOP-like） were 77.5% （31/40）, 84.8% （56/66） and 45.4% （50/110）, respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine （P〈0.05）. However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients （91.7% vs 81.0%, P=0.306）. Compared with CEP12 negative patients, there were no significant differences in progression-free survival （PFS） （χ^2=0.410, P=0.478） and overall survival （OS） （χ^2=0.052, P=0.180） for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 （95%CI 15.4-31.7） and 118.5 （95%CI 74.5-162.4） month while the 5-year PFS and OS were （52.9±7.6）% and （74.8±6.6）%.ConclusionsCEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.ConclusionsCEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.