Changes of immunophenotype in children with acute B lymphoblastic leukemia after induction chemotherapy and its clinical significance

doi:10.3877/cma.j.issn.2095-5820.2018.04.006

Abstract

Abstract:

Objective

To investigate the changes in antigen expressions on leukemic cells and its effect on prognosis at the end of induction in children with acute lymphoblastic leukemia (ALL).

Methods

The retrospective study included 691 children diagnosed with B-ALL between 2010 and 2015. The bone marrow specimens of the children were used for the detection of leukemia immunophenotype at the first diagnosis, and for the detection of minimal residual disease (MRD) at the 33rd day of treatment. Among them, 155 patients with MRD greater than 0.01% were included in this study. The immunophenotypic changes of leukemia cells were studied by using a four-color monoclonal fluorescent antibody combination through multi-parameter flow cytometry.

Results

86 of 155 (55.5%) cases showed phenotype shifts at least one marker. CD19 was the most stable markers. However, nearly one third of the children had significant differences in CD20 expression on the 33rd day of initial diagnosis and chemotherapy. Changes in antigen expression were not significantly correlated with event-free survival (EFS), relapse-free survival (RFS) or overall survival (OS) (P>0.05). Multivariate analysis showed that white blood cell (WBC) and BCR-ABL had independent prognostic value in ALL.

Conclusion

Although changes in antigen expression were common at the end of induction remission therapy, they were not associated with prognostic value in patients with MRD positive on day 33 of chemotherapy.

Key words: Acute lymphoblastic leukemia, Flow cytometry, Pediatric, Immunophenotype

Qingkai Dai, Huan Peng, Lan Chen, Qi Chen, Yongmei Jiang. Changes of immunophenotype in children with acute B lymphoblastic leukemia after induction chemotherapy and its clinical significance[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2018, 06(04): 216-221.

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References 40

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变量		结果
年龄(中位数，范围)(岁)		4(1-15)
性别(N，%)		?
?	男	90(58.1%)
?	女	65(41.9%)
危险度(N，%)		?
?	低危	37(23.9%)
?	中危	95(61.3%)
?	高危	23(14.8%)
实验室检查(中位数，范围)		?
?	WBC(×10⁹/L)	10.0(1.0-601.2)
?	HGB(g/L)	75(29-148)
?	PLT(×10⁹/L)	55(3-644)
?	中性粒细胞计数(×10⁹/L)	1.1(0-54.1)
?	外周血原幼淋巴细胞(×10⁹/L)	3.1(0-550.0)
?	骨髓原幼淋巴细胞(%)	87.5(26.0-97.5)
FAB分型(N，%)		?
?	L1型	64(41.3%)
?	L2型	91(58.7%)
初诊免疫分型(N，%)		?
?	Pro-B	15(9.7%)
?	Common	108(69.7%)
?	Pre-B	32(20.6%)
细胞遗传学异常(N，%)		?
?	BCR-ABL	12(7.7%)
?	MLL-AF4	3(1.9%)
?	TEL-AML1	23(14.8%)
?	E2A-PBX1	8(5.2%)

变量		结果
年龄(中位数，范围)(岁)		4(1-15)
性别(N，%)		?
?	男	90(58.1%)
?	女	65(41.9%)
危险度(N，%)		?
?	低危	37(23.9%)
?	中危	95(61.3%)
?	高危	23(14.8%)
实验室检查(中位数，范围)		?
?	WBC(×10⁹/L)	10.0(1.0-601.2)
?	HGB(g/L)	75(29-148)
?	PLT(×10⁹/L)	55(3-644)
?	中性粒细胞计数(×10⁹/L)	1.1(0-54.1)
?	外周血原幼淋巴细胞(×10⁹/L)	3.1(0-550.0)
?	骨髓原幼淋巴细胞(%)	87.5(26.0-97.5)
FAB分型(N，%)		?
?	L1型	64(41.3%)
?	L2型	91(58.7%)
初诊免疫分型(N，%)		?
?	Pro-B	15(9.7%)
?	Common	108(69.7%)
?	Pre-B	32(20.6%)
细胞遗传学异常(N，%)		?
?	BCR-ABL	12(7.7%)
?	MLL-AF4	3(1.9%)
?	TEL-AML1	23(14.8%)
?	E2A-PBX1	8(5.2%)

免疫表型的变化		例数(%)	EFS(%)		P	RFS(%)		P	OS(%)		P
免疫表型的变化		例数(%)	3年	5年	P	3年	5年	P	3年	5年	P
CD10		?	?	?	0.264	?	?	0.314	?	?	0.356
?	无变化	139(89.7%)	81.4	71.9	?	82.3	74.8	?	83.8	76.9	?
?	获得	1(0.6%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
?	丢失	15(9.7%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
CD19		?	?	?	-	?	?	-	?	?	-
?	无变化	155(100.0%)	83.2	75.0	?	84.1	77.7	?	85.3	79.4	?
?	获得	0(0.0%)	-	-	?	-	-	?	-	-	?
?	丢失	0(0.0%)	-	-	?	-	-	?	-	-	?
CD20		?	?	?	0.264	?	?	0.148	?	?	0.212
?	无变化	100(64.5%)	81.3	74.6	?	81.9	77.8	?	82.5	73.3	?
?	获得	38(24.5%)	90.9	90.9	?	93.3	93.3	?	97.4	97.4	?
?	丢失	17(11.0%)	75.0	50.0	?	75.0	50.0	?	73.8	73.8	?
CD22		?	?	?	0.727	?	?	0.758	?	?	0.790
?	无变化	152(98.1%)	83.1	75.0	?	84.1	77.6	?	85.3	79.4	?
?	获得	0(0.0%)	-	-	?	-	-	?	-	-	?
?	丢失	3(1.9%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
CD34		?	?	?	0.821	?	?	0.685	?	?	0.629
?	无变化	133(85.8%)	82.9	74.9	?	86.5	78.2	?	85.4	80.6	?
?	获得	9(5.8%)	75.0	75.0	?	75.0	75.0	?	75.0	75.0	?
?	丢失	13(8.4%)	91.7	76.4	?	76.4	76.4	?	91.7	76.4	?
CD45		?	?	?	0.251	?	?	0.257	?	?	0.285
?	无变化	129(83.2%)	82.6	72.6	?	83.7	75.7	?	85.1	77.7	?
?	获得	18(11.6%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
?	丢失	8(5.2%)	68.6	68.6	?	68.6	68.6	?	68.6	68.6	?

免疫表型的变化		例数(%)	EFS(%)		P	RFS(%)		P	OS(%)		P
免疫表型的变化		例数(%)	3年	5年	P	3年	5年	P	3年	5年	P
CD10		?	?	?	0.264	?	?	0.314	?	?	0.356
?	无变化	139(89.7%)	81.4	71.9	?	82.3	74.8	?	83.8	76.9	?
?	获得	1(0.6%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
?	丢失	15(9.7%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
CD19		?	?	?	-	?	?	-	?	?	-
?	无变化	155(100.0%)	83.2	75.0	?	84.1	77.7	?	85.3	79.4	?
?	获得	0(0.0%)	-	-	?	-	-	?	-	-	?
?	丢失	0(0.0%)	-	-	?	-	-	?	-	-	?
CD20		?	?	?	0.264	?	?	0.148	?	?	0.212
?	无变化	100(64.5%)	81.3	74.6	?	81.9	77.8	?	82.5	73.3	?
?	获得	38(24.5%)	90.9	90.9	?	93.3	93.3	?	97.4	97.4	?
?	丢失	17(11.0%)	75.0	50.0	?	75.0	50.0	?	73.8	73.8	?
CD22		?	?	?	0.727	?	?	0.758	?	?	0.790
?	无变化	152(98.1%)	83.1	75.0	?	84.1	77.6	?	85.3	79.4	?
?	获得	0(0.0%)	-	-	?	-	-	?	-	-	?
?	丢失	3(1.9%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
CD34		?	?	?	0.821	?	?	0.685	?	?	0.629
?	无变化	133(85.8%)	82.9	74.9	?	86.5	78.2	?	85.4	80.6	?
?	获得	9(5.8%)	75.0	75.0	?	75.0	75.0	?	75.0	75.0	?
?	丢失	13(8.4%)	91.7	76.4	?	76.4	76.4	?	91.7	76.4	?
CD45		?	?	?	0.251	?	?	0.257	?	?	0.285
?	无变化	129(83.2%)	82.6	72.6	?	83.7	75.7	?	85.1	77.7	?
?	获得	18(11.6%)	100.0	100.0	?	100.0	100.0	?	100.0	100.0	?
?	丢失	8(5.2%)	68.6	68.6	?	68.6	68.6	?	68.6	68.6	?

抗原	初诊时表达(N)	诱导缓解化疗后^a(N)			复发^b(N)
抗原	初诊时表达(N)	无变化	获得	丢失	无变化	获得	丢失
CD10	15	0	0	0	0	0	0
CD19	17	0	0	0	0	0	0
CD20	11	4	1	3	4	2	2
CD22	17	0	0	0	0	0	0
CD34	12	4	2	2	1	0	1
CD45	12	2	0	2	4	2	2

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