儿童急性淋巴细胞白血病治疗失败相关因素分析

doi:10.12372/jcp.2023.22e0067

Abstract

Abstract:

Objective To explore the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). Methods The clinical data of 124 newly diagnosed ALL children with treatment failure admitted from January 2013 to December 2017 were retrospective analyzed. The association of different clinical features with recurrence time and sites was compared and the possible risk factors for treatment failure was analyzed. Results By April 15, 2020, the median follow-up time was 24.0 (14.0-43.5) months. Among the 124 children who failed treatment, 82 were boys and 42 were girls. The median age at first diagnosis was 8.0 (3.3-13.0) years. The reasons for treatment failure included recurrence (104 cases), non-recurrent death (19 cases) and secondary tumor (1 case). Totally 104 ALL children relapsed, whose median recurrence time was 17.7 (3.0-57.2) months. Very early recurrence (52 cases) was the commonest recurrence time, and bone marrow (84 cases) was the commonest recurrence site. The recurrence time was correlated with initial white blood cell count, immunophenotyping, different fusion genes and risk stratifications (P<0.05). The recurrence site was correlated with initial white blood cell count and immunophenotyping (P<0.05). MRD level on day 33 was an independent risk factor for treatment failure survival rate (TFS) and overall survival (OS) rate (P<0.05). Conclusions Recurrence is the main cause of treatment failure in children with ALL. Close monitoring of early treatment response, active prevention and treatment of very early recurrence can reduce the incidence of treatment failure and improve the OS rate of children with ALL.

Key words: acute lymphoblastic leukemia, treatment failure, recurrence, minimal residual disease, child

XUE Yujuan, LU Aidong, WANG Yu, JIA Yueping, ZUO Yingxi, ZHANG Leping. Clinical analysis of treatment failure in children with acute lymphoblastic leukemia[J].Journal of Clinical Pediatrics, 2023, 41(3): 204-209.

Figures/Tables 3

临床特征	例数	复发时间					复发部位
临床特征	例数	极早期	早期	晚期	χ²值	P	骨髓	中枢神经系统	骨髓+中枢神经系统	其他髓外复发	χ²值	P
性别					2.25	0.324					-	0.619¹⁾
男	73	33(45.2)	27(37.0)	13(17.8)			58(79.5)	5(6.8)	8(11.0)	2(2.7)
女	31	19(61.3)	8(25.8)	4(12.9)			26(83.9)	3(9.7)	1(3.2)	1(3.2)
年龄/岁					0.43	0.808					-	0.791¹⁾
≥10	44	23(52.3)	15(34.1)	6(13.6)			34(77.3)	4(9.1)	5(11.4)	1(2.3)
1~10	60	29(48.3)	20(33.3)	11(18.3)			50(83.3)	4(6.7)	4(6.7)	2(3.3)
初诊WBC×10⁹·L^-1					7.53	0.023					-	0.011¹⁾
≥50.0	33	23(69.7)	7(21.2)	3(9.1)			23(69.7)	3(9.1)	7(21.2)	0(0.0)
<50.0	71	29(40.8)	28(39.4)	14(19.7)			61(85.9)	5(7.0)	2(2.8)	3(4.2)
免疫分型					-	0.019¹⁾					-	0.016¹⁾
B-ALL	88	39(44.3)	32(36.4)	17(19.3)			74(84.1)	7(8.0)	4(4.5)	3(3.4)
T-ALL	16	13(81.3)	3(18.8)	0(0.0)			10(62.5)	1(6.3)	5(31.3)	0(0.0)
融合基因					-	0.022¹⁾					-	0.545¹⁾
ETV6-RUNX1⁺	6	0(0.0)	4(66.7)	2(33.3)			5(83.3)	0(0.0)	0(0.0)	1(16.7)
MLL⁺	2	1(50.0)	0(0.0)	1(50.0)			2(100.0)	0(0.0)	0(0.0)	0(0.0)
E2A-PBX1⁺	8	4(50.0)	1(12.5)	3(37.5)			6(75.0)	2(25.0)	0(0.0)	0(0.0)
BCR-ABL1⁺	9	7(77.8)	2(22.2)	0(0.0)			7(77.8)	1(11.1)	1(11.1)	0(0.0)
其他	79	40(50.6)	28(35.4)	11(13.9)			64(81.0)	5(6.3)	8(10.1)	2(2.5)
第15天骨髓原始幼稚淋巴细胞/%					1.71	0.426					-	0.819¹⁾
<5.0	44	21(47.7)	13(29.5)	10(22.7)			34(77.3)	4(9.1)	5(11.4)	1(2.3)
≥5.0	46	27(58.7)	13(28.3)	6(13.0)			39(84.8)	3(6.5)	3(6.5)	1(2.2)
未检测	14	4(28.6)	9(64.3)	1(7.1)			11(78.6)	1(7.1)	1(7.1)	1(7.1)
第33天MRD/%					3.35	0.780					-	0.879¹⁾
≥1.0	21	11(52.4)	7(33.3)	3(14.3)			17(81.0)	1(4.8)	2(9.5)	1(4.8)
0.1~1.0	24	14(58.3)	5(20.8)	5(20.8)			22(91.7)	1(4.2)	1(4.2)	0(0.0)
0.01~0.1	10	4(40.0)	5(50.0)	1(10.0)			9(90.0)	0(0)	1(10.0)	0(0.0)
<0.01	49	23(46.9)	18(36.7)	8(16.3)			36(73.5)	6(12.2)	5(10.2)	2(4.1)
第90天MRD/%					-	0.129¹⁾					-	0.336¹⁾
≥0.1	17	13(76.5)	3(17.6)	1(5.9)			16(94.1)	0(0.0)	0(0.0)	1(5.9)
0.01~0.1	10	6(60.0)	2(20.0)	2(20.0)			10(100.0)	0(0.0)	0(0.0)	0(0.0)
<0.01	77	33(42.9)	30(39.0)	14(18.2)			58(75.3)	8(10.4)	9(11.7)	2(2.6)
复发部位					-	0.321¹⁾					-	-
骨髓	84	45(53.6)	25(29.8)	14(16.7)			-	-	-
中枢神经系统	8	3(37.5)	3(37.5)	2(25)			-	-	-
骨髓+中枢神经系统	9	4(44.4)	4(44.4)	1(11.1)			-	-	-
其他髓外复发	3	0(0.0)	3(100.0)	0(0.0)
危险度					-	0.029¹⁾					-	0.053¹⁾
标危	11	2(18.2)	7(63.6)	2(18.2)			8(72.7)	0(0.0)	1(9.1)	2(18.2)
中危	52	23(44.2)	18(34.6)	11(21.2)			41(78.8)	7(13.5)	4(7.7)	0(0.0)
高危	41	27(65.9)	10(24.4)	4(9.8)			35(85.4)	1(2.4)	4(9.8)	1(2.4)

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预后因素	失败例数	3年OS率/%	χ²值	P	3年TFS率/%	χ²值	P
性别			0.25	0.621		1.91	0.167
男	82	87.2±1.7			81.7±2.0
女	42	87.0±2.1			84.9±2.3
年龄/岁			15.00	0.001		11.82	0.003
≥10	54	79.3±2.9			75.3±3.1
1~10	70	90.6±1.4			86.3±1.6
初诊WBC×10⁹·L^-1			10.41	0.001		10.60	0.001
≥50.0	39	77.9±3.6			73.6±3.8
<50.0	85	89.7±1.4			85.5±1.6
免疫分型			12.98	<0.001		7.04	0.008
T-ALL	23	72.8±5.1			70.3±5.2
B-ALL	101	89.1±1.3			84.7±1.5
融合基因			38.42	<0.001		38.85	<0.001
ETV6/RUNX1⁺	6	97.8±1.6			95.7±2.1
MLL⁺	3	91.7±5.6			91.7±5.6
E2A/PBX1⁺	11	89.7±4.9			79.5±6.5
BCR/ABL1⁺	13	77.7±5.9			74.0±6.2
其他	91	85.6±1.8			81.1±2.0
伴髓外浸润			7.42	0.006		3.69	0.055
是	13	74.4±6.7			74.4±6.7
否	111	88.0±1.4			83.6±1.5
第15天骨髓原始幼稚淋巴细胞/%¹⁾			23.63	<0.001		32.23	<0.001
≥5.0	55	78.2±3.2			70.5±3.5
<5.0	52	92.0±1.4			89.4±1.6
第33天MRD/%²⁾			80.00	<0.001		76.43	<0.001
≥1.0	27	55.9±7.0			52.0±7.1
0.1~1.0	25	77.6±5.1			70.1±5.6
0.01~0.1	10	89.3±3.8			87.1±4.0
<0.01	59	92.3±1.3			88.3±1.5
90天MRD/%³⁾			47.29	<0.001		55.68	<0.001
≥0.1	18	53.1±8.8			46.9±8.8
0.01~0.1	10	76.0±8.5			68.0±9.3
<0.01	92	90.1±1.3			86.2±1.5
危险度分层			53.46	<0.001		47.01	<0.001
标危	13	97.0±1.3			93.6±1.9
中危	60	88.7±1.8			84.0±2.1
高危	51	70.8±3.8			66.7±4.0

Clinical analysis of treatment failure in children with acute lymphoblastic leukemia

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