EAC动员方案在淋巴瘤自体造血干细胞移植中的应用研究

摘要/Abstract

摘要：

目的探讨EAC动员方案(依托泊苷+阿糖胞苷+环磷酰胺)在淋巴瘤患者自体造血干细胞移植(ASCT)中动员采集造血干细胞的安全性和有效性。方法回顾性分析2018年6月至2020年3月在中国医学科学院北京协和医学院肿瘤医院深圳医院经过EAC方案或环磷酰胺方案联合粒细胞集落刺激因子(G-CSF)动员采集外周血干细胞的36例淋巴瘤患者,其中16例采用EAC方案(EAC组),20例采用环磷酰胺方案(环磷酰胺组)。当白细胞≤1.0×10⁹/L时给予G-CSF,每天10 μg/kg,分两次皮下注射,观察动员采集过程中血液学指标变化、采集细胞数量、不良反应及ASCT后造血重建情况。结果EAC组和环磷酰胺组化疗后分别使用G-CSF动员中位天数5 d(3~8 d)、7 d(4~12 d)后开始外周血干细胞采集,采集成功率分别为100%(16/16)和75.0%(15/20),采集优良率分别为87.5%(14/16)、25.0%(5/20),差异均具有统计学意义(P=0.041;P<0.001);两组采集CD34⁺细胞中位数分别为13.67×10⁶/kg、3.45×10⁶/kg,单个核细胞数中位数分别为7.16×10⁸/kg、5.09×10⁸/kg,CD34⁺细胞/单个核细胞数分别为1.44%、0.67%,差异均具有统计学意义(Z=-4.219,P<0.001;Z=-2.118,P=0.034;Z=-3.104,P=0.002)。EAC组和环磷酰胺组≥3级粒细胞减少发生率分别为100%(16/16)和90.0%(18/20),≥3级血红蛋白下降发生率分别为43.8%(7/16)和25.0%(5/20),≥3级血小板减少发生率分别为87.5%(14/16)和65.0%(13/20),差异均无统计学意义(P=0.492;P=0.298;P=0.245)。两组感染、消化系统不良反应及其他不良反应发生率差异亦无统计学意义(均P>0.05)。所有患者后续ASCT均采用改良BuCy方案预处理,EAC组患者移植后中性粒细胞中位植入时间为9.0 d,血小板中位植入时间为10.5 d;环磷酰胺组分别为12.0 d、13.5 d,差异均具有统计学意义(Z=-4.698,P<0.001;Z=-3.757,P<0.001)。结论EAC动员方案可显著提高造血干细胞采集数目,优良采集成功率高,不良反应可控,值得临床推广应用。

关键词:淋巴瘤,EAC动员方案,外周血干细胞采集,自体造血干细胞移植,造血重建

Abstract:

ObjectiveTo explore the safety and efficacy of EAC [etoposide+cytarabine+cyclophosphamide (CTX)] mobilization scheme for mobilizing stem cells in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation (ASCT).MethodsA total of 36 patients with lymphoma who had collected peripheral blood stem cells through EAC or CTX+granulocyte colony stimulating factor (G-CSF) mobilization scheme in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to March 2020 were retrospectively analyzed. Among them, 16 patients used EAC mobilization (EAC group), and 20 patients used CTX (CTX group). When white blood cells≤1.0×10⁹/L, G-CSF (10 μg/kg per day) was given subcutaneously in two doses. The changes of hematology indexes, the number of collected cells, adverse reactions during mobilization collection and hematopoietic reconstitution after ASCT were observed.ResultsThe peripheral blood stem cells were collected on 5 d (3-8 d) after EAC+G-CSF mobilization and 7 d (4-12 d) after CTX+G-CSF mobilization. The success rates of collection in the EAC group and CTX group were 100% (16/16) and 75.0% (15/20) respectively, the high-quality collection rates were 87.5% (14/16) and 25.0% (5/20) respectively, and there were statistically significant differences (P=0.041; P<0.001). The median of CD34⁺cells of the two groups was 13.67×10⁶/kg and 3.45×10⁶/kg respectively, the median of mononuclear cells was 7.16×10⁸/kg and 5.09×10⁸/kg respectively, the median of CD34⁺cells/mononuclear cells was 1.44% and 0.67% respectively, and there were statistically significant differences (Z=-4.219,P<0.001;Z=-2.118,P=0.034;Z=-3.104,P=0.002). In the EAC group and CTX group, the incidences of grade 3 and above granulocytopenia were 100% (16/16) and 90.0% (18/20) respectively, the incidences of grade 3 and above hemoglobin reduction were 43.8% (7/16) and 25.0% (5/20) respectively, the incidences of grade 3 and above thrombocytopenia were 87.5% (14/16) and 65.0% (13/20) respectively, and there were no statistically significant differences (P=0.492;P=0.298;P=0.245). There were no significant differences in the incidences of infection, adverse reactions of digestive system or other adverse reactions between the two groups (allP>0.05). All patients accepted improved Bucy scheme before ASCT. The median implantation time of neutrophils and platelets was 9.0 d and 10.5 d in the EAC group, which was 12.0 d and 13.5 d in the CTX group, and there were statistically significant differences (Z=-4.698,P<0.001;Z=-3.757,P<0.001).ConclusionEAC mobilization scheme can significantly increase the number of hematopoietic stem cell. This scheme has a high success rate of high-quality collection and the adverse reactions are within the controllable range. It provides a high-quality mobilization scheme for hematopoietic stem cell mobilization and collection, which is worthy of clinical promotion and application.

Key words:Lymphoma,EAC mobilization scheme,Peripheral blood stem cell collection,Autologous hematopoietic stem cell transplantation,Hematopoietic reconstitution

陈丽娜, 郭智, 刘玄勇, 陈晓, 张弋慧智, 李旭绵, 韦丽娅, 王月乔, 谢晶. EAC动员方案在淋巴瘤自体造血干细胞移植中的应用研究[J]. 国际肿瘤学杂志, 2021, 48(11): 666-672.

Chen Lina, Guo Zhi, Liu Xuanyong, Chen Xiao, Zhang Yihuizhi, Li Xumian, Wei Liya, Wang Yueqiao, Xie Jing. Application study of EAC mobilization scheme in autologous hematopoietic stem cell transplantation of lymphoma[J]. Journal of International Oncology, 2021, 48(11): 666-672.

图/表4

表1

两种动员方案淋巴瘤患者一般资料比较[例(%)]"

一般资料	EAC组 (n=16)	环磷酰胺组 (n=20)	χ²/Z值	P值	一般资料	EAC组 (n=16)	环磷酰胺组 (n=20)	χ²/Z值	P值
性别					全身症状^a
男	12(75.0)	11(55.0)	-	0.301		无	9(56.3)	13(65.0)	-	0.734
女	4(25.0)	9(45.0)				有	7(43.8)	7(35.0)
年龄(岁)						是否骨髓浸润
≤50	11(68.8)	13(65.0)	-	0.549		是	4(25.0)	2(10.0)	-	0.374
>50	5(31.3)	7(35.0)				否	12(75.0)	18(90.0)
淋巴瘤类型						动员前疾病状态
HL	3(18.8)	2(10.0)				完全缓解	10(62.5)	16(80.0)	-	0.285
DLBCL	7(43.8)	9(45.0)				部分缓解	6(37.5)	4(20.0)
MCL	3(18.8)	4(20.0)	1.407	0.989		动员前化疗次数
HGBL	1(6.3)	2(10.0)				≤4次	5(31.2)	6(30.0)	-	0.609
PTCL	1(6.3)	2(10.0)				>4次	11(68.8)	14(70.0)
PMBL	1(6.3)	1(5.0)				动员前环磷酰胺使用次数
Ann Arbor分期						动员前环磷酰胺使用次数
Ⅳ期	11(68.8)	16(80.0)				≤4次	9(56.3)	8(40.0)	-	0.503
Ⅲ期	1(6.3)	2(10.0)	-0.880	0.379		>4次	7(43.8)	12(60.0)
Ⅱ期	2(12.5)	1(5.0)				G-CSF使用天数
Ⅰ期	2(12.5)	1(5.0)				≤4 d	13(81.3)	5(25.0)	-	0.002
						>4 d	3(18.8)	15(75.0)

表1

项目	EAC组(n=16)	环磷酰胺组(n=20)	Z值	P值
CD34⁺细胞数	13.67(5.85,45.56)×10⁶/kg	3.45(1.92,4.95)×10⁶/kg	-4.219	<0.001
单个核细胞数	7.16(5.60,12.34)×10⁸/kg	5.09(3.87,8.14)×10⁸/kg	-2.118	0.034
CD34⁺细胞/单个核细胞数	1.44%(0.70%,4.08%)	0.67%(0.30%,0.98%)	-3.104	0.002
采集成功与否
采集成功	16(100)	15(75.0)	-	0.041
采集失败	0(0)	5(25.0)
采集优良与否
优良	14(87.5)	5(25.0)	-	<0.001
未达优良	2(12.5)	15(75.0)

表2

图1

表3

两种动员方案淋巴瘤患者动员采集相关不良反应比较[例(%)]"

不良反应	EAC组 (n=16)	环磷酰胺组 (n=20)	Z值	P值
血液系统不良反应粒细胞减少
≤2级	0(0)	2(10.0)	-	0.492
≥3级	16(100)	18(90.0)
血红蛋白下降
≤2级	9(56.2)	15(75.0)	-	0.298
≥3级	7(43.8)	5(25.0)
血小板减少
≤2级	2(12.5)	7(35.0)	-	0.245
≥3级	14(87.5)	13(65.0)
非血液系统不良反应感染
无	7(43.8)	10(50.0)
轻度	7(43.8)	2(10.0)	-0.681	0.496
中度	2(12.5)	4(20.0)
重度	0(0)	4(20.0)
消化系统不良反应
无	11(68.7)	8(40.0)
Ⅰ~Ⅱ级	5(31.3)	9(45.0)	-1.911	0.056
Ⅲ~Ⅳ级	0(0)	3(15.0)
口唇疱疹	1(6.3)	0(0)	-	0.444
水肿	1(6.3)	3(15.0)	-	0.613
乏力	1(6.3)	6(30.0)	-	0.104
转氨酶升高	2(12.5)	2(10.0)	-	0.608
骨痛	2(12.5)	5(25.0)	-	0.426
口唇或四肢麻木	2(12.5)	4(20.0)	-	0.672

表3

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