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
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.
J Cai, J Yu, X Zhu, S Hu, Y Zhu, H Jiang, C Li, Y Fang, C Liang, X Ju, X Tian, X Zhai, J Hao, Q Hu, N Wang, H Jiang, L Sun, CK Li, K Pan, M Yang, S Shen, C Cheng, RC Ribeiro, CH Pui, J; Chinese Children’s Cancer Group childhood acute lymphoblastic leukaemia (ALL) 2015 study group (CCCG-ALL-2015) Tang. Treatment abandonment in childhood acute lymphoblastic leukaemia in China: a retrospective cohort study of the Chinese Children’s Cancer Group. Arch Dis Child 2019; 104(6): 522–529 https://doi.org/10.1136/archdischild-2018-316181
pmid: 30705079
4
M Betensky, K Kulkarni, M Rizzi, S Jones, LR Brandão, EVS Faustino, NA Goldenberg, A Sharathkumar. Recommendations for standardized definitions, clinical assessment, and future research in pediatric clinically unsuspected venous thromboembolism: communication from the ISTH SSC subcommittee on pediatric and neonatal thrombosis and hemostasis. J Thromb Haemost 2022; 20(7): 1729–1734 https://doi.org/10.1111/jth.15731
pmid: 35570328
5
UH Athale, C Laverdiere, T Nayiager, YL Delva, G Foster, L Thabane, AK Chan. Evaluation for inherited and acquired prothrombotic defects predisposing to symptomatic thromboembolism in children with acute lymphoblastic leukemia: a protocol for a prospective, observational, cohort study. BMC Cancer 2017; 17(1): 313 https://doi.org/10.1186/s12885-017-3306-5
pmid: 28472942
6
U Nowak-Göttl, G Kenet, LG Mitchell. Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment. Best Pract Res Clin Haematol 2009; 22(1): 103–114 https://doi.org/10.1016/j.beha.2009.01.003
pmid: 19285277
7
G Goyal, VR Bhatt. L-asparaginase and venous thromboembolism in acute lymphocytic leukemia. Future Oncol 2015; 11(17): 2459–2470 https://doi.org/10.2217/fon.15.114
pmid: 26274336
8
V Caruso, L Iacoviello, A Di Castelnuovo, S Storti, G Mariani, G de Gaetano, MB Donati. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 2006; 108(7): 2216–2222 https://doi.org/10.1182/blood-2006-04-015511
pmid: 16804111
9
S Ranta, R Tuckuviene, A Mäkipernaa, BK Albertsen, T Frisk, U Tedgård, ÓG Jónsson, K Pruunsild, Andersson N Gretenkort, Gunnes M Winther, Trakymiene S Saulyte, T Frandsen, M Heyman, E Ruud, J Helgestad. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia—a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. Br J Haematol 2015; 168(4): 547–552 https://doi.org/10.1111/bjh.13162
pmid: 25288392
10
K Vu, NV Luong, J Hubbard, A Zalpour, S Faderl, DA Thomas, D Yang, H Kantarjian, MH Kroll. A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center. Cancer Med 2015; 4(1): 27–35 https://doi.org/10.1002/cam4.332
pmid: 25487644
11
F Rühle, M Stoll. Advances in predicting venous thromboembolism risk in children. Br J Haematol 2018; 180(5): 654–665 https://doi.org/10.1111/bjh.15060
pmid: 29265336
12
S Riondino, P Ferroni, FM Zanzotto, M Roselli, F Guadagni. Predicting VTE in cancer patients: candidate biomarkers and risk assessment models. Cancers (Basel) 2019; 11(1): E95 https://doi.org/10.3390/cancers11010095
pmid: 30650562
13
CU Rank, N Toft, R Tuckuviene, K Grell, OJ Nielsen, TL Frandsen, HVH Marquart, BK Albertsen, U Tedgård, H Hallböök, E Ruud, KB Jarvis, P Quist-Paulsen, P Huttunen, U Wartiovaara-Kautto, ÓG Jónsson, SS Trakymiene, L Griškevičius, K Saks, M Punab, K Schmiegelow. Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood 2018; 131(22): 2475–2484 https://doi.org/10.1182/blood-2018-01-827949
pmid: 29661787
14
ILM Klaassen, MN Lauw, M Fiocco, IM van der Sluis, R Pieters, S Middeldorp, MD van de Wetering, HA de Groot-Kruseman, CH van Ommen. Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: risk factors and effect on prognosis. Res Pract Thromb Haemost 2019; 3(2): 234–241 https://doi.org/10.1002/rth2.12182
pmid: 31011707
15
P Giordano, N Santoro, GC Del Vecchio, C Rizzari, G Masera, D De Mattia. T-immunophenotype is associated with an increased prevalence of thrombosis in children with acute lymphoblastic leukemia. A retrospective study. Haematologica 2003; 88(9): 1079–1080
pmid: 12969822
16
Y Zhu, R Yang, J Cai, J Yu, Y Tang, Y Chen, N Wang, H He, X Wu, FWT Cheng, L Sun, Y He, X Ju, X Tian, Q Hu, R Jin, K Pan, Y Fang, X Zhai, H Jiang, CK Li. Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: a multicenter study CCCG-ALL-2015. Cancer Med 2020; 9(6): 2113–2121 https://doi.org/10.1002/cam4.2889
pmid: 31994344
KP Cohoon, AA Ashrani, DJ Crusan, TM Petterson, KR Bailey, JA Heit. Is infection an independent risk factor for venous thromboembolism? A population-based, case-control study. Am J Med 2018; 131(3): 307–316.e2 https://doi.org/10.1016/j.amjmed.2017.09.015
pmid: 28987552
19
E Truelove, AK Fielding, BJ Hunt. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia. Leukemia 2013; 27(3): 553–559 https://doi.org/10.1038/leu.2012.290
pmid: 23099335
N Kraaijpoel, Nisio M Di, FI Mulder, Es N van, J Beyer-Westendorf, M Carrier, D Garcia, M Grosso, AK Kakkar, MF Mercuri, S Middeldorp, CR Hernandez, A Santamaria, L Schwocho, A Segers, P Verhamme, TF Wang, JI Weitz, G Zhang, JI Zwicker, HR Büller, GE Raskob. Clinical impact of bleeding in cancer-associated venous thromboembolism: results from the Hokusai VTE Cancer Study. Thromb Haemost 2018; 118(8): 1439–1449 https://doi.org/10.1055/s-0038-1667001
pmid: 30060256
22
H Stevens, K Peter, H Tran, J McFadyen. Predicting the risk of recurrent venous thromboembolism: current challenges and future opportunities. J Clin Med 2020; 9(5): E1582 https://doi.org/10.3390/jcm9051582
pmid: 32456008
