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Frontiers of Medicine

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Front. Med.    2023, Vol. 17 Issue (3) : 518-526    https://doi.org/10.1007/s11684-022-0958-6
RESEARCH ARTICLE
Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children’s Cancer Group-ALL-2015
Mengmeng Yin1, Hongsheng Wang2, Xianmin Guan4, Ju Gao5, Minghua Yang6, Ningling Wang7, Tianfeng Liu8, Jingyan Tang3, Alex WK Leung9, Fen Zhou10, Xuedong Wu11, Jie Huang12, Hong Li13, Shaoyan Hu14, Xin Tian15, Hua Jiang16, Jiaoyang Cai3, Xiaowen Zhai2(), Shuhong Shen3(), Qun Hu1()
1. Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2. Department of Hematology/Oncology, Children’s Hospital of Fudan University, Shanghai 201100, China
3. Department of Hematology/Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Key Laboratory of Pediatric Hematology & Oncology of China Ministry of Health, Shanghai 200120, China
4. Department of Hematology/Oncology, Chongqing Medical University Affiliated Children’s Hospital, Chongqing 400015, China
5. Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
6. Department of Pediatrics, Xiangya Hospital Central South University, Changsha 410008, China
7. Department of Pediatrics, Anhui Medical University Second Affiliated Hospital, Hefei 230601, China
8. State Key Laboratory of Experimental Hematology and Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300020, China
9. Department of Pediatrics, Hong Kong Children’s Hospital, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
10. Department of Pediatrics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
11. Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou 516006, China
12. Department of Hematology/Oncology, Children’s Hospital of Nanjing Medical University, Nanjing 210008, China
13. Department of Hematology/Oncology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
14. Department of Hematology/Oncology, Children’s Hospital of Soochow University, Suzhou 215002, China
15. Department of Hematology/Oncology, Kunming Children’s Hospital, Kunming 650103, China
16. Department of Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou 510620, China
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Abstract

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children’s Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08–2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12–18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Keywords acute lymphoblastic leukemia      child      venous thromboembolism      epidemiology      clinical characteristic      risk factor     
Corresponding Author(s): Xiaowen Zhai,Shuhong Shen,Qun Hu   
Just Accepted Date: 11 January 2023   Online First Date: 15 February 2023    Issue Date: 28 July 2023
 Cite this article:   
Mengmeng Yin,Hongsheng Wang,Xianmin Guan, et al. Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children’s Cancer Group-ALL-2015[J]. Front. Med., 2023, 17(3): 518-526.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0958-6
https://academic.hep.com.cn/fmd/EN/Y2023/V17/I3/518
Fig.1  Occurrence of VTE during the chemotherapy phase.
Characteristic N = 7640 VTE (N = 159) P value
Gender 0.859
Male 4521 93 (2.06%)
Female 3119 66 (2.12%)
Age, year 0.027*
0 < age < 12 7111 141 (1.98%)
12 ≤ age < 18 529 18 (3.40%)
Immunophenotyping 0.015*
T-ALL 724 24 (3.31%)
B-ALL 6916 135 (1.95%)
Clinical risk 0.788
LR 3948 78 (1.98%)
IR 3543 78 (2.20%)
HR 149 3 (2.01%)
Mediastinal mass 0.032*
Yes 285 11 (3.86%)
No 7355 148 (2.01%)
BCR/ABL1 0.687
Positive 335 8 (2.39%)
Negative 7305 151 (2.07%)
WBC 0.755
≤50 × 109/L 6026 127 (2.11%)
> 50 × 109/L 1614 32 (1.98%)
Septicemia < 0.001*
Yes 1204 41 (25.79%)
No 6436 118 (74.21%)
Tab.1  Patient characteristics
Variable Multivariable OR 95% CI for OR P value
Lower Upper
Age ≥ 12 years 1.402 0.811 2.422 0.226
T-ALL 1.742 1.084 2.801 0.022*
Mediastinal mass 0.857 0.379 1.940 0.711
Tab.2  Risk factors for VTE
Catheter type N CRT Non-CRT P value
Major 0.006*
PICC 110 79 (71.82%) 31 (28.18%)
CVC 35 33 (94.29%) 2 (5.71%)
Other
PORT 5 4 (80.00%) 1 (20.00%)
Hickman-catheter 2 1 (50.00%) 1 (50.00%)
Broviac catheter 2 2 (100.00%) 0 (0.00%)
Medium-length catheter 1 1 (100.00%) 0 (0.00%)
Tab.3  CRT and non-CRT distribution based on catheter type
Fig.2  VTE location.
Characteristic Symptomatic VTE (N = 93) Asymptomatic VTE (N = 66) P value
Sex 0.434
Male 52 (55.91%) 41 (62.12%)
Female 41 (44.09%) 25 (37.88%)
Age, year 0.023*
0 < age < 12 78 (83.87%) 63 (95.45%)
12 ≤ age < 18 15 (16.13%) 3 (4.60%)
CRT < 0.001*
Yes 60 (64.52%) 60 (90.91%)
No 33 (35.48%) 6 (9.09%)
VTE location < 0.001*
Brain 26 (27.96%) 2 (3.03%)
Other 67 (72.04%) 64 (96.97%)
Tab.4  Clinical characteristics of symptomatic VTE
Factor VTE recur (N = 8) VTE not recur (N = 151) P value
Gender 0.180
Male 7 (87.50%) 86 (56.95%)
Female 1 (12.50%) 65 (44.05%)
Immunophenotyping 0.767
T-ALL 2 (25.00%) 22 (15.23%)
B-ALL 6 (75.00%) 129 (84.77%)
CRT 1.000
Yes 6 (75.00%) 114 (75.50%)
No 2 (25.00%) 37 (24.50%)
Symptomatic VTE 0.109
Yes 2 (25.00%) 91 (60.26%)
No 6 (75.00%) 60 (39.74%)
Septicemia 0.641
Yes 1 (12.50%) 40 (26.49%)
No 7 (87.50%) 111 (73.51%)
Non-ultrasound-guided venous intubation 0.02*
Yes 6 (75.00%) 43 (29.25%)
No 2 (25.00%) 104 (70.75%)
Residual thrombus 0.006*
Yes 4 (50.00%) 16 (10.60%)
No 4 (50.00%) 135 (89.40%)
Catheter removal 1.000
Yes 2 (25.00%) 47 (31.13%)
No 6 (75.00%) 104 (68.87%)
Tab.5  VTE recur and associated factors
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