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[荧光原位杂交检测70例伴12号染色体三体慢性淋巴细胞白血病患者的临床分析]

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

作者信息

Lyu R, Li Z J, Li H, Yi S H, Liu W, Wang T Y, Xiong W J, Qiu L G

机构信息

Department of Lymphoma, Institute of Hematology & Blood Disease Hospital, State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2018 May 14;39(5):387-391. doi: 10.3760/cma.j.issn.0253-2727.2018.05.008.

Abstract

To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Clinical 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). Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% 4.0%, =0.011) and LDH>247 U/L (43.3% 18.5%, (2)=15.892, <0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β(2)-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% 12.7%, (2)=4.730, =0.030), and lower ratio of CD23 (95.2% 99.6%, =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 (<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% 81.0%, =0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) ((2)=0.410, =0.478) and overall survival (OS) ((2)=0.052, =0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95% 15.4-31.7) and 118.5 (95% 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%. CEP12 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.

摘要

运用荧光原位杂交技术(FISH,检测12号染色体着丝粒,即CEP12)总结并研究12号染色体三体慢性淋巴细胞白血病(CLL)患者的特征、预后及治疗情况。回顾性分析2003年5月至2015年4月期间330例CLL患者的临床资料,采用FISH(CEP12)检测12号染色体三体情况。将CEP12阳性患者(70例)与CEP12阴性患者(260例)的临床资料及实验室特征进行比较。与CEP12阴性CLL患者相比,CEP12阳性CLL患者肝肿大比例(13.6%对4.0%,P = 0.011)及乳酸脱氢酶(LDH)>247 U/L的比例(43.3%对18.5%,χ(2)=15.892,P < 0.001)分别显著更高。这两个亚组在年龄、性别、临床分期、β2微球蛋白水平、免疫球蛋白重链可变区(IGHV)突变率及脾肿大/淋巴结肿大方面无显著差异。然而,与CEP12阴性患者相比,CEP12阳性患者FMC7比例更高(23.8%对12.7%,χ(2)=4.730,P = 0.030),而CD23比例更低(95.2%对99.6%,P = 0.033)。氟达拉滨(不含利妥昔单抗)、利妥昔单抗(含或不含氟达拉滨)及传统化疗组(苯丁酸氮芥、CHOP或类CHOP方案)的总缓解率(ORR)分别为77.5%(31/40)、84.8%(56/66)及45.4%(50/110)。传统化疗组的ORR低于氟达拉滨组和利妥昔单抗组。对于CEP12阳性患者,仅使用氟达拉滨时ORR低于CEP12阴性患者(P<0.05)。然而,使用利妥昔单抗时,差异可消除,且CEP12阴性患者的ORR甚至略高(91.7%对81.0%,P = 0.306)。与CEP12阴性患者相比,CEP12阳性患者的无进展生存期(PFS)(χ(2)=0.410,P = 0.478)和总生存期(OS)(χ(2)=0.052,P = 0.180)无显著差异,CEP12阳性患者从诊断到开始治疗的中位时间及OS时间分别为22.6(95%CI 15.4 - 31.7)个月和118.5(95%CI 74.5 - 162.4)个月,5年PFS和OS分别为(52.9±7.6)%和(74.8±6.6)%。CEP12阳性CLL患者肝肿大及LDH水平较高更为常见。传统化疗疗效最低,单用氟达拉滨的疗效不如CEP12阴性患者,但使用利妥昔单抗时疗效相当。

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