探讨Double/Triple Hit淋巴瘤的流式免疫表型特征在疾病诊断及生存结局相关性中的应用

Study on the Application of Flow Immunophenotype Characteristics of Double/Triple Hit Lymphoma in the Correlation Between Disease Diagnosis and Survival Outcomes

目的确立二次或三次打击淋巴瘤(Double/Triple-Hit lymphoma,D/THL)流式免疫表型特征,研究与B淋巴细胞白血病(B-LBL)在免疫表型上的差异,并探讨流式免疫表型特征与D/THL生存结局的相关性。方法采用多色FCI分析法对40例D/THL患者和25 B-LBL患者的样本的免疫表型进行检测和评价,并将流式免疫表型结果与基因亚型以及总体生存率进行统计学对比分析。结果 90%(36/40)的D/THL病例CD10表达呈阳性,近一半病例(48%,19/40)缺乏表面轻链。45%(18/40)的病例CD45表达呈弱阳性,40%(16/40) CD19表达呈弱阳性,43%(17/40) CD20表达呈弱阳性。28%(11/40)显示伴随CD19和CD20的弱表达,38%(15/40)的CD19和CD20表达呈差异化表达(variable expression)。在不同基因亚型之间,除Dim CD45和BCL2阳性发生率达有差异外(BCL2+/MYC+组Dim CD45发生率明显低于BCL2+/BCL6+/MYC+组(P=0.03); BCL2+/MYC+组中bcl2阳性率为96%,而其它基因亚型组阳性率均为0%),其它表型发生率差异均无统计学意义(P>0. 05)。与B-LBL相比,B-LBL的CD45和CD20低表达发生率明显高于D/THL(X^2=20.78、20.83,); CD19和CD20同时弱表达在D/THL发生率稍多(28%D/THL vs. 10%B-LBL),但差异无统计学意义(X^2=2.31)。B-LBL的TdT阳性发生率明显高于D/THL(X^2=30.74,)。对30例已经死亡患者进行了生存分析显示,不同基因型总体生存率无显著性差异(BCL2+MYC+对BCL6+/MYC+,P=0.08; BCL2+MYC+对BCL2+/BCL6+/MYC+,P=0.13; BCL6+/MYC+对BCL2+/BCL6+/MYC+,P=1.0); Dim CD45和Bcl2阳性预示着与较低的总体生存率(X_1~2=L11.2,10.4,P=0.01,0.015)。结论 D/THL流式免疫表型特征研究有助于D/THL鉴别诊断。对流式免疫表型与疾病结局的生存分析结果,将有利于临床对D/THL整体预后进行危险分层管理,以便能针对特定病人及时采取个体化治疗。

Objective To establish the flow immunophenotype characteristics of Double/Triple-Hit lymphoma(D/THL),study the differences in immunophenotype with B-lymphoblastic leukemia (B-LBL),and explore the correlation between flow immunophenotype characteristics and D/THL survival outcomes.Methods The immunophenotype of 40 patients with D/THL and 25 patients with B-LBL were detected and evaluated by Multicolor FCI analysis,and the results of flow immunophenotype were statistically compared with those of gene subtype and overall survival rate.Results In the D/THL group,90%(36/40) of the cases showed positive CD10 expression;nearly half of the cases (48%,19/40) lacked superficial light chains;45%(18/40) of the cases expressed weak positive CD45 expression;40%(16/40) of the cases expressed weak positive CD19 expression;43%(17/40) of the cases expressed weak positive CD20 expression.With 28%(11/40) of the cases low expression of CD19 and CD20,38%(15/40) of the cases was variable expression of CD19 and CD20.In different genotype subtypes,the positive incidence of dim CD45 and BCL2 was different,while there was no statistically significant difference in the incidence of other phenotypes.The incidence of Dim CD45 in BCL2+/MYC+ Group was significantly lower than that of BCL2+/BCL6+/MYC+ Group (p=0.03).And the positive rate of bcl2 in BCL2+/MYC+ Group was 96%,while that of other genotype groups was 0%.Compared with the B-LBL group,the incidence of low expression of CD45 and CD20 in B-LBL group was significantly higher than that of D/THL (=20.78、20.83),and the incidence of weak expression of both CD19 and CD20 in D/THL group was slightly higher (28% in D/THL group and 10% in B-LBL group),no statistically significant difference (χ^2=2.31).The positive incidence of TDT in B-LBL group was significantly higher than that in D/THL group (χ^2=30.74).The survival analysis of 30 deceased patients showed that there was no statistically significant difference in the overall survival rate of different genotypes (BCL2+/MYC+ group and BCL6+/MYC+ group,P=0.08;BCL2+/MYC+ group and BCL2+/BCL6+/MYC+ group,P=0.13;BCL6+/MYC+ group and BCL2+/BCL6+/MYC+ group,P=1.0);and Dim CD45 and Bcl2 positive indicated a lower overall survival rate (L2=11.2,10.4,P=0.01,0.015).Conclusion The study of D/THL flow immunophenotype is helpful to D/THL differential diagnosis.The results of survival analysis of convective immunophenotype and disease outcome will be beneficial to the clinical prognosis of D/THL.