初诊低危组儿童急性淋巴细胞白血病远期复发影响因素：基于单中心254例患儿的5年随访分析

doi:10.12372/jcp.2026.25e0888

Abstract

Abstract:

Objective To investigate the overall long-term prognosis and associated influencing factors in children with newly diagnosed low-risk acute lymphoblastic leukemia (ALL), and to provide evidence for precision stratified treatment strategies. Methods Clinical data of 254 children with newly diagnosed low-risk ALL admitted to our institution between January 2009 and December 2019 were retrospectively analyzed. Among them, 111 patients were treated with the CCCG-ALL 2009 protocol (from January 2009 to March 2015), and 143 with the CCCG-ALL 2015 protocol (from April 2015 to December 2019). Clinical characteristics, dynamic minimal residual disease (MRD) monitoring data, and follow-up outcomes were collected. Survival analyses were performed using Kaplan-Meier curves, with intergroup comparisons via the Log-rank test. Independent prognostic factors were identified using Cox proportional hazards regression models. Results The median age of included patients was 3 (1-13) years, with a median follow-up duration of 94 (1-186) months. The 5-year relapse-free survival (RFS) and overall survival (OS) rates were (88.3±2.0)% and (94.0±1.5)%, respectively; the 10-year RFS and OS rates were (86.0±2.3)% and (93.2±1.7)%, respectively. No statistically significant differences were observed in overall 5-year RFS or OS between the CCCG-ALL 2009 and 2015 protocol groups (all P>0.05). However,in the TEL/AML1-positive subgroup, the 2015 protocol group exhibited significantly superior 5-year RFS compared to the 2009 group (95.3% vs.76.8%, P=0.047). Univariate analysis revealed that bone marrow non-remission on day 19, MRD≥1.0% on day 19, and MRD≥0.01% post-consolidation were associated with adverse prognosis (all P<0.05). Multivariate Cox regression confirmed that post-consolidation MRD≥0.01% was an independent risk factor for RFS (HR=2.348, 95% CI: 1.040-5.300, P=0.040). The overall recurrence rate was 12.9%, with isolated bone marrow recurrence accounting for 66.7% of cases. The 5-year OS after salvage therapy in patients with isolated bone marrow recurrence (63.7%) was significantly lower than that in those with isolated extramedullary or combined recurrence (100%, P=0.045). Conclusions Children with newly diagnosed low-risk ALL have a favorable overall long-term prognosis. Post-consolidation MRD≥0.01% is an independent prognostic risk factor for this population. Dynamic MRD monitoring facilitates the identification of high-risk subsets and guides treatment intensification. The optimized CCCG-ALL 2015 protocol maintains therapeutic efficacy while potentially reducing treatment-related toxicity.

Key words: acute lymphoblastic leukemia, child, low risk, minimal residual disease, prognosis

CLC Number:

WANG Zhen, SHAO Jingbo, ZHANG Na, XIA Min, ZHU Jiashi, DU Chengkan, LI Hong. Factors influencing long-term recurrence in pediatric acute lymphoblastic leukemia patients with low-risk disease at initial diagnosis: a five-year follow-up analysis of 254 cases from a single center[J].Journal of Clinical Pediatrics, 2026, 44(7): 628-635.

Figures/Tables 5

Table 1

Kaplan-Meier analysis of prognostic factors for survival in children with newly diagnosed low risk ALL"

项目	例数(%)	RFS率（ x±E）/%	χ²值	P	OS率（ x±E）/%	χ²值	P
性别			2.07	0.150		0.14	0.700
男	138（54.3）	83.7±3.2			94.1±2.0
女	116（45.7）	88.8±3.3			92.2±2.8
年龄			0.32	0.571		0.80	0.370
<3岁	200（78.7）	87.2±2.4			92.3±2.0
≥3岁	54（21.3）	87.0±5.2			96.3±2.6
初诊WBC计数			0.67	0.411		0.31	0.576
<30×10⁹/L	249（98.0）	88.1±2.1			93.1±1.7
≥30×10⁹/L	5（2.0）	100			100
初诊血红蛋白			0.54	0.460		0.17	0.673
<100 g/L	213（83.8）	87.4±2.3			92.8±1.9
≥100 g/L	41（16.2）	90.2±4.6			95.1±3.4
初诊血小板计数			2.63	0.104		2.23	0.135
<100×10⁹/L	162（63.7）	84.7±2.9			91.2±2.4
≥100×10⁹/L	92（36.3）	90.1±3.4			96.7±1.9
免疫分型			1.47	0.478		2.33	0.311
Pro-B	2（0.8）	100.0			100.0
Common-B	209（82.2）	88.8±2.2			94.6±1.6
Pre-B	43（17.0）	80.4±6.2			87.1±5.5
Pred/Dex早期治疗反应			0.34	0.560		1.34	0.246
好	91（57.5）	88.3±2.7			92.0±3.4
不佳	67（42.5）	84.4±3.7			87.8±4.1
治疗方案			0.14	0.708		3.43	0.064
2009方案	111（43.7）	85.2±3.4			90.1±2.8
2015方案	143（56.3）	87.6±2.8			96.5±1.5
第19天骨髓是否缓解			8.53	0.003		18.94	<0.001
缓解	247（97.2）	89.2±2.0			94.2±1.6
未缓解	7（2.8）	57.1±18.7			57.1±18.7
D19 MRD			4.06	0.044		10.11	0.001
<1.0%	230（90.6）	89.3±2.1			95.6±1.4
≥1.0%	24（9.4）	73.9±9.3			79.2±8.3
巩固后MRD			6.07	0.014		16.15	<0.001
<0.01%	224（88.1）	89.4±2.1			95.9±1.3
≥0.01%	30（11.9）	72.3±8.3			75.6±8.1
TEL/AML1融合基因			0.03	0.845		0.31	0.576
阳性	80（31.4）	84.8±4.7			93.4±3.5
阴性	174（68.6）	86.4±2.6			93.0±1.9
高二倍体			2.02	0.155		0.12	0.721
是	41（16.1）	79.2±6.6			92.7±4.1
否	213（83.9）	89.5±2.1			93.4±1.8
CNS状态			0.75	0.686		2.26	0.323
正常	247（97.2）	87.6±2.1			93.9±1.5
CNS2	4（1.5）	50.0±35.4			50.0±35.4
损伤	3（1.3）	100			100

Table 1

Figure 1

Figure 2

Table 2

Table 3

References 19

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项目	例数(n)	2009方案组例数[n/%]	2015方案组例数[n/%]	χ²值	P
性别				0.03	0.860
男	138	61（44.2）	77（55.8）
女	116	50（43.1）	66（56.9）
年龄				0.01	0.901
<3岁	200	87（43.5）	113（56.6）
≥3岁	54	24（44.4）	30（55.6）
初诊白细胞计数				1.16	0.281
<30×10⁹/L	249	110（44.2）	139（55.8）
≥30×10⁹/L	5	1（20.0）	4（80.0）
TEL/AML1融合基因				0.08	0.777
阳性	80	36（45.0）	44（55.0）
阴性	174	75（43.1）	99（56.9）
高二倍体				2.85	0.091
是	41	13（31.7）	28（68.3）
否	213	98（46.0）	115（54.0）

因素	β	SE	Wald χ²	HR	95%CI	P
第19天骨髓是否缓解
缓解				1
未缓解	1.180	0.673	3.071	3.253	0.870~12.171	0.080
D19 MRD
<0.1%				1
≥1.0%	0.416	0.519	0.642	1.516	0.548~4.192	0.432
巩固后MRD
<0.01%				1
≥0.01%	0.854	0.415	4.223	2.348	1.040~5.300	0.040

Factors influencing long-term recurrence in pediatric acute lymphoblastic leukemia patients with low-risk disease at initial diagnosis: a five-year follow-up analysis of 254 cases from a single center

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