CD56抗原表达在急性早幼粒细胞白血病中的临床意义和预后分析

何杰; 董海波; 张启国; 周荣富; 许景艳; 杨永公; 许佩佩; 张谦; 陈兰昕; 周敏; 袁翠英; 蒋如如; 刘锦雯; 欧阳建; 陈兵; 曾慧

doi:10.13201/j.issn.1004-2806.2023.07.010

CD56抗原表达在急性早幼粒细胞白血病中的临床意义和预后分析

- 南京大学医学院附属鼓楼医院血液科(南京，210008)

详细信息

通讯作者: 曾慧，E-mail：Zenghui_7908@163.com

中图分类号: R733.71

收稿日期: 2022-07-13

修回日期: 2023-04-12

刊出日期: 2023-07-01

Clinical significance and prognostic analysis of CD56 antigen expression in acute promyelocytic leukemia

- Department of Hematology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

More Information

Corresponding author: ZENG Hui, E-mail: Zenghui_7908@163.com

Received Date: 13 July 2022

Revised Date: 12 April 2023

Publish Date: 01 July 2023

摘要

摘要: 目的分析CD56抗原在初诊急性早幼粒细胞白血病(acute promyelocytic leukemia，APL)中的表达及其与临床参数之间的相关性，探究该抗原的临床意义及对预后的影响。方法回顾性分析169例初诊APL患者的临床数据，按照CD56抗原表达状况，将其分为CD56阳性和CD56阴性组，比较2组患者性别、年龄、体能状态(ECOG)、血细胞计数、生化指标、凝血功能、骨髓及外周血早幼粒细胞比例、免疫分型、危险分层、FLT3突变、染色体核型、PML/RAR α异聚体类型及融合率、FAB分型(M3a/M3b/M3v)、弥散性血管内凝血(disseminated intravascular coagulation，DIC)积分等参数有无差异。以达分子学缓解(molecular complete remission，mCR)的时间为界，将临床事件分为早期事件(分化综合征、QT间期延长、出血、栓塞、死亡)和晚期事件(继发第二肿瘤、QT间期延长、出血、疾病复发、死亡)，比较2组早晚期事件发生率的差异。探索CD56阳性表达对总生存期(OS)、无进展生存期(PFS)及无事件生存期(EFS)的影响。结果 169例APL患者中，17例患者CD56阳性，该抗原的阳性表达率为10.1%。CD56阳性和阴性患者在D-二聚体水平和共表达CD64抗原方面比较，差异有统计学意义(P=0.016，0.017)。CD56阳性组患者达mCR时间更长(P=0.023)，2组患者的早期事件发生率差异无统计学意义，2组患者的疾病复发事件差异有统计学意义(P=0.014)。中位随访63.0个月，CD56阳性患者具有更差的OS、PFS和EFS(P=0.023，0.004，< 0.001)。多因素分析显示CD56阳性是PFS、EFS的独立不良因素(P=0.018，< 0.001)。结论 CD56阳性是APL的预后不良因素，临床医师需根据该抗原的表达与否决定APL患者的全程管理策略。
- 急性早幼粒细胞白血病 /
- CD56抗原表达 /
- 临床特征 /
- 预后分析
Abstract: Objective To analyze the expression of CD56 antigen in newly diagnosed acute promyelocytic leukemia(acute promyelocytic leukemia, APL) and its correlation with clinical parameters, and to explore the clinical significance of this antigen and its influence on the prognosis.Methods Clinical data from 169 patients with new diagnosis APL in our hospital were retrospectively analyzed. According to the expression of CD56 antigen, patients were divided into CD56 positive group and CD56 negative group. The gender, age, ECOG, blood cell count, biochemical criterion, coagulation function, bone marrow and peripheral blood promyelocytic proportions, immunophenotype, risk stratification, FLT3 mutation, chromosome karyotype, PML/RAR α heteromer type and fusion rate, FAB type(M3a/M3b/M3v), disseminated intravascular coagulation(DIC) score were compared between the two groups. Based on the time to molecular complete remission(mCR), clinical events were divided into early events(differentiation syndrome, QT prolongation, bleeding, embolism, death) and late events(secondary tumor, QT prolongation, bleeding, disease recurrence, death), and the difference in the incidence of early and late events was compared. To explore the effects of CD56 positive expression on overall survival(OS), progression-free survival(PFS) and event-free survival(EFS).Results Among 169 patients with APL, 17 patients were positive for CD56, and the positive expression rate was 10.1%. There were significant differences in D-dimer level(P=0.016) and expression of CD64 antigen(P=0.017). CD56 positive group had longer time to reach mCR(P=0.023), and no significant difference was observed in the incidence of early events, while the incidence of disease recurrence event was distinctly different between the two groups(P=0.014). With a median follow-up period of 63.0 months, CD56 positive patients had worse OS, PFS, and EFS(P=0.023, 0.004, < 0.001). Multivariate analysis suggested that the expression of CD56 was an independent adverse factor of PFS and EFS(P=0.018, < 0.001).Conclusion CD56 positive expression is a poor prognostic factor of APL, and clinicians should determine the long-term management strategy of APL patients according to the expression of this antigen.
- acute promyelocytic leukemia /
- CD56 antigen expression /
- clinical features /
- prognostic analysis

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图 1 169例APL患者Kaplan-Meier生存分析

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表 1 CD56阳性和CD56阴性APL患者的基线特征

特征	CD56阳性(n=17)	CD56阴性(n=152)	P
男/例(%)	7(41.2)	67(44.1)	1.000
年龄/岁	34.0(23.0~64.0)	43.0(16.0~75.0)	0.987
ECOG评分≥2分/例(%)	7(41.2)	68(44.7)	0.804
白细胞计数/(×10⁹/L)	3.0(1.5，18.0)	2.4(1.1，13.5)	0.384
贫血 < 60 g/L/例(%)	1(5.9)	24(15.8)	0.465^a
血小板计数/(×10⁹/L)	37.0(26.0，54.0)	27.0(14.3，49.0)	0.162
LDH/(U/L)	252.0(185.0，488.0)	285.0(195.0，475.0)	0.800
低白蛋白血症 < 35 g/L/例(%)	0	15(9.9)	0.368^b
甘油三酯/(mmol/L)	1.8(1.3，2.4)	1.7(1.1，2.5)	0.638
胆固醇/(mmol/L)	4.5(4.0，5.2)	4.2(3.5，4.9)	0.101
APTT/s	28.2(24.2，33.6)	26.7(24.7，29.8)	0.270
PT/s	15.0(12.6，15.5)	13.5(12.5，15.0)	0.249
纤维蛋白原/(g/L)	0.9(0.8，1.7)	1.3(0.8，1.8)	0.177
D-二聚体/(mg/L)	20.9(4.2，32.3)	6.4(2.8，16.3)	0.016
骨髓早幼粒细胞比例/%	85.5(76.6，91.3)	84.0(74.8，90.5)	0.826
外周血早幼粒细胞比例/%	65.0(20.5，91.5)	39.0(2.3，74.8)	0.124
CD2阳性/例(%)	3(17.6)	12(7.9)	0.373^a
CD7阳性/例(%)	1(5.9)	9(5.9)	1.000^a
CD11b阳性/例(%)	1(5.9)	18(11.8)	0.739^a
CD15阳性/例(%)	2(11.8)	20(13.2)	1.000^a
CD19阳性/例(%)	2(11.8)	3(2.0)	0.135^a
CD34阳性/例(%)	5(29.4)	21(13.8)	0.182^a
CD64阳性/例(%)	13(76.5)	65(42.8)	0.017^a
CD117阳性/例(%)	15(88.2)	141(92.8)	0.854^a
HLA-DR阳性/例(%)	1(5.9)	15(9.9)	0.924^a
危险分层/例(%)			0.578
低中危	11(64.7)	109(71.7)
高危	6(35.3)	43(28.3)
FLT3突变/例(%)			1.000^a
无	13(76.5)	118(77.6)
有	4(23.5)	34(22.4)
染色体核型/例(%)			0.854^a
良好+正常	13(76.5)	124(81.6)
异常+复杂	4(23.5)	28(18.4)
类型/例(%)			0.062
1型+2型	7(41.2)	100(65.8)
3型	10(58.8)	52(34.2)
融合率/%	86.0(75.0，93.8)	79.5(64.1，91.9)	0.115
FAB分型/例(%)			1.000^b
3a+3b	17(100.0)	147(96.7)
3v	0	5(3.3)
DIC积分/例(%)			0.994^a
< 5分	1(5.9)	14(9.2)
≥5分	16(94.1)	138(90.8)
^a连续校正的χ²检验；^bFisher's检验。

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表 2 单因素Cox回归分析

因素	OS		PFS		EFS
因素	P	HR(95%CI)	P	HR(95%CI)	P	HR(95%CI)
女性	0.035	0.321(0.111~0.924)	0.033	0.345(0.129~0.920)	0.976	0.986(0.375~2.590)
年龄>60岁	0.145	2.545(0.725~8.934)	0.215	2.191(0.634~7.569)	0.663	1.388(0.317~6.072)
ECOG评分≥2分	0.019	3.874(1.249~12.018)	0.017	3.501(1.248~9.822)	0.625	1.268(0.489~3.287)
白细胞计数>10×10⁹/L	0.047	2.695(1.011~7.185)	0.026	2.857(1.133~7.204)	0.316	1.664(0.615~4.501)
贫血 < 60 g/L	0.741	1.236(0.352~4.342)	0.871	1.108(0.321~3.830)	0.783	1.192(0.342~4.150)
血小板计数 < 40×10⁹/L	0.446	1.644(0.458~5.898)	0.197	2.261(0.654~7.813)	0.498	1.473(0.480~4.519)
CD2阳性	0.081	3.094(0.870~10.999)	0.153	2.477(0.714~8.591)	0.471	1.725(0.392~7.584)
CD7阳性	0.134	3.139(0.703~14.021)	0.230	2.465(0.565~10.756)	0.795	1.308(0.173~9.891)
CD11b阳性	0.632	1.442(0.322~6.454)	0.885	1.114(0.255~4.864)	0.214	2.216(0.633~7.764)
CD15阳性	0.389	0.411(0.054~3.113)	0.314	0.355(0.047~2.669)	0.302	0.345(0.046~2.601)
CD19阳性	0.663	0.048(0~41 871.343)	0.643	0.048(0~18 512.361)	0.399	2.396(0.315~18.228)
CD56阳性	0.033	3.458(1.109~10.785)	0.008	4.051(1.434~11.446)	< 0.001	7.059(2.573~19.366)
CD34阳性	0.020	3.320(1.206~9.139)	0.007	3.712(1.436~9.593)	0.024	3.158(1.166~8.551)
CD64阳性	0.436	0.654(0.224~1.907)	0.436	0.676(0.252~1.811)	0.279	1.700(0.651~4.442)
CD117阳性	0.001	0.174(0.060~0.501)	0.002	0.190(0.067~0.533)	0.334	0.483(0.110~2.113)
HLA-DR阳性	0.525	1.622(0.366~7.194)	0.725	1.303(0.299~5.678)	0.410	0.043(0~76.287)
危险分层，高危	0.055	2.607(0.978~6.948)	0.033	2.732(1.084~6.887)	0.365	1.584(0.585~4.284)
FLT基因突变	0.018	3.307(1.227~8.914)	0.046	2.628(1.017~6.790)	0.947	0.959(0.275~3.339)
类型，3型	0.035	2.972(1.080~8.180)	0.027	2.917(1.130~7.532)	0.281	1.690(0.652~4.381)
染色体状态，异常+复杂	0.232	1.908(0.668~5.500)	0.122	2.168(0.813~5.779)	0.021	3.129(1.191~8.220)
形态学，3v	0.323	2.782(0.366~21.124)	0.422	2.284(0.304~17.189)	0.655	0.048(0~29 174.387)
低白蛋白血症 < 35 g/L	0.703	0.675(0.089~5.111)	0.614	0.595(0.079~4.474)	0.630	0.609(0.081~4.591)
LDH升高>245 U/L	0.024	5.480(1.245~24.118)	0.013	6.480(1.489~28.197)	0.402	1.531(0.566~4.139)
低胆固醇 < 2.90 mmol/L	0.876	0.851(0.112~6.442)	0.762	0.732(0.097~5.5023)	0.433	0.044(0~109.041)
高甘油三酯>1.70 mmol/L	0.275	1.758(0.639~4.839)	0.545	1.333(0.526~3.378)	0.433	1.333(0.526~3.378)
低纤维蛋白原 < 1.0 g/L	0.051	2.683(0.998~7.213)	0.047	2.562(1.011~6.494)	0.729	1.183(0.456~3.068)
D-二聚体升高>正常值5倍	0.127	4.854(0.639~36.879)	0.106	5.285(0.702~39.773)	0.145	31.969(0.301~3 391.894)
PT时间延长≥3 s	0.002	7.261(2.066~25.522)	0.002	7.162(2.069~24.784)	0.392	2.417(0.320~18.235)

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表 3 多因素Cox回归分析

因素	OS		PFS		EFS
因素	P	HR(95%CI)	P	HR(95%CI)	P	HR(95%CI)
女性	0.038	0.264(0.075~0.930)	0.036	0.288(0.090~0.920)	-	-
ECOG评分≥2分	0.157	2.515(0.701~9.028)	0.142	2.389(0.747~7.638)	-	-
白细胞计数>10×10⁹/L	0.774	0.832(0.237~2.923)	0.951	657.495(0~+∞)	-	-
CD56阳性	0.057	3.567(0.964~13.206)	0.018	4.503(1.294~15.670)	< 0.001	7.376(2.644~20.572)
CD34阳性	0.316	1.944(0.530~7.135)	0.275	1.974(0.582~6.700)	0.059	2.617(0.965~7.101)
CD117阳性	0.039	0.225(0.055~0.925)	0.029	0.205(0.049~0.853)	-	-
危险分层，高危	-	-	0.950	0.001(0~+∞)	-	-
FLT基因突变	0.217	2.162(0.636~7.350)	0.599	1.370(0.423~4.439)	-	-
类型，3型	0.916	0.934(0.264~3.307)	0.968	1.024(0.319~3.290)	-	-
染色体状态，异常+复杂	-	-	-	-	0.019	3.214(1.209~8.545)
LDH升高>245 U/L	0.146	3.545(0.645~19.491)	0.062	4.939(0.921~26.494)	-	-
低纤维蛋白原 < 1.0 g/L	-	-	0.718	1.223(0.410~3.652)	-	-
PT时间延长≥3 s	0.866	1.167(0.194~7.023)	0.846	1.189(0.207~6.823)	-	-

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