8例Richter综合征临床及生物学特征分析

为了探讨Richter综合征（RS）临床及生物学特征及其预后因素,回顾性分析8例RS患者。利用血清学检测、多参数流式细胞术（FCM）、常规细胞遗传学（CC）、间期荧光原位杂交（FISH）技术、PCR联合DNA序列测定,分别检测患者血清乳酸脱氢酶（LDH）、β2-微球蛋白（β2-MG）、胸苷激酶1（TK1）、血清铁蛋白（SF）和糖链抗原-125（CA-125）,CD38和ZAP-70,染色体核型,ATM和p53基因缺失、＋12异常,以及免疫球蛋白重链可变区（IgVH）突变。结果显示：8例RS患者中7例转化为弥漫大B细胞淋巴瘤（DLBCL）,1例转化为霍奇金淋巴瘤（HL）。7例LDH高于正常值,4例β2-MG高于正常值,7例SF高于正常值,4例CA-125高于正常值,1例TK1高于正常值。4例患者ZAP-70阳性,7例CD38阳性,5例IgVH无突变,4例有染色体复杂核型,1例有＋12,1例有p53缺失。按就诊时BinetA＋B期与BinetC期将患者分为两组,BinetA＋B组从诊断至转化的平均时间为98.5个月,BinetC组为38.3个月,两组间有显著性差异（p=0.021）。平均总生存期（OS）在BinetA＋B组及BinetC组之间分别是123.8个月及49.8个月,两组间有显著性差异（p=0.049）,转化后平均生存时间分别是34.5个月及10.3个月。结论：RS患者血清LDH、β2-MG和SF水平高,ZAP-70和CD38高表达、IgVH无突变发生率高,临床分期可能是RS转化的风险及预后因素。

Clinical and Biological Features of 8 Patients with Richter's Syndrome

In order to evaluate the clinical,biological features and prognostic factors of Richter＇s syndrome（RS）,8 RS patients were analyzed restrospectively. The serological test,multiplex parameter flow cytometry,conventional cytogenetic analysis,FISH technique and PCR combined with sequence detection were used to detect the LDH,β2-MG,TK1,SF,CA125,ZAP-70,chromosome karyotype,ATM and p53 gene deletion,as well as ＋12 abnormality and IgVH mutation. The results indicated that 7 out of 8 patients transformed to diffuse large B cell lymphoma （DLBCL） and 1 patient transformd to Hodgkin lymphoma （HL）. Among 8 patients,LDH level in 7 patients,β2-MG level in 4 patients,SF level in 7 patients,CA-125 level in 4 patients and TK1 level in 1 patient exceeded the normal range. Meanwhile,ZAP-70 and CD38 were expressed positively in 4 and 7 out of 8 patients respectively. Unmutated IgVH was found in 5 patients,and 4 patients had the complex chromosome abnormalities. ＋12 and p53 deletion was found in 1 patient. 8 patients were divided into two groups （Binet A＋B and Binet C）,the mean time from diagnosis to progression was 98.5 months in Binet A＋B group,compared with 38.3 months in Binet C group,there was significant difference between two groups（p=0.021）. Mean overall survival was 123.8 months and 49.8 months in two groups,respectively （p=0.049）. The mean survival after transformation was 34.5 months in Binet A＋B group and 10.3 months in Binet C group. In conclusion,the level of LDH,β2-MG and SF are higher in RS patients in Binet C group,and so are the incidence of high expressed ZAP-70 and CD 38,unmutated IgVH. The clinical stage may be the risk and prognostic factors for RS transformation.