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Semin Thromb Hemost
DOI: 10.1055/a-2575-7359
Original Article

Magnetic Resonance Screening for Cerebral Venous Sinus Thrombosis during Treatment with Pegaspargase

Xiao Zhang   *
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Yang Fu    *
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Hongsheng Wang 
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Xiaohua Zhu
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Yi Yu
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Junye Jiang
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Ping Cao
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Xiaowen Qian
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Chen Shen
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
,
Xiaowen Zhai
1   Department of Hematology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, People's Republic of China
› Author Affiliations Funding This study was supported by the National Key R&D Program of China (no. 2022YFC2705003), National Natural Science Foundation of China (no. 82141125), Science and Technology Commission of Shanghai Municipality (no. 21Y31900302), and Children's Hospital of Fudan University Clinical Postdoctoral Program of “Future Medical Scientists.”
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Abstract

In children with leukemia, cerebral venous sinus thrombosis (CVST) has a significant incidence and mortality rate, which may interfere with the chemotherapy process and lead to long-term neurological complications. However, large studies and population-based data on CVST in children are scarce. This study aims to characterize pediatric CVST associated with pegaspargase (PEG-ASP) and evaluate the significance of magnetic resonance venography (MRV) screening following induction remission in acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). We present a retrospective cohort of a total of 27 children with CSVT and ALL/LBL. The study covers a 4-year period for MRV screening following induction remission and an 8-year comparison period, involving 716 children treated at the Department of Hematology, Children's Hospital of Fudan University. The detection rate of CVST significantly increased after MRV screening (8.4% vs. 1.6%, p < 0.01). Over half (58%) of the CVST cases were asymptomatic. Male (84% vs. 52%, p = 0.008), immune subtype of T (37% vs. 10%, p = 0.001) and higher initial platelet counts (196.25 ± 140.67 vs. 112.49 ± 115.62, p = 0.02) patients were more likely to develop CVST. The common symptoms were headache (56%), seizures (31%), vomiting (13%), lethargy (13%), coma (6%), hallucinations (6%), and schizophrenia (6%). Symptomatic patients had a higher likelihood of transverse sinus involvement (75% vs. 9%, p = 0.006). Asymptomatic patients had shorter treatment durations (25.5 ± 16.7 weeks vs. 51.6 ± 25.8 weeks, p = 0.02) and fewer long-term complications (50% vs. 0%, p = 0.02). Thromboelastographic amplitude values at 30 minutes after maximum amplitude were significantly higher in symptomatic patients (49.4 ± 13.2 vs. 35.1 ± 8.3, p = 0.01). This study highlights a significant incidence of PEG-ASP-related CVST in children, with MRV screening revealing a notably higher detection rate than previously reported. Most cases were asymptomatic, which demonstrated better prognoses, emphasizing the importance of MRV for early CVST diagnosis after induction remission in ALL/LBL.

Keywords

pegasparaginase - cerebral venous sinus thrombosis - magnetic resonance venography - acute lymphoblastic leukemia - lymphoblastic lymphoma

* These authors contributed equally and share the first authorship.




Publication History

Received: 09 December 2024

Accepted: 04 April 2025

Article published online:
25 April 2025

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  • References

  • 1 Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010; 36 (04) 277-285
    PubMedSearch in Google Scholar
  • 2 Gatta G, Botta L, Rossi S. et al; EUROCARE Working Group. Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5–a population-based study. Lancet Oncol 2014; 15 (01) 35-47
    CrossrefPubMedSearch in Google Scholar
  • 3 Cooperation Group of Phase II Clinical Trial of PEG-Asp. Comparison of polyethylene glycol conjugated asparaginase and L-asparaginase for treatment of childhood acute lymphoblastic leukemia. Zhonghua Xue Ye Xue Za Zhi 2008; 29 (01) 29-33
    PubMedSearch in Google Scholar
  • 4 Mitchell L, Hoogendoorn H, Giles AR, Vegh P, Andrew M. Increased endogenous thrombin generation in children with acute lymphoblastic leukemia: risk of thrombotic complications in L'Asparaginase-induced antithrombin III deficiency. Blood 1994; 83 (02) 386-391
    CrossrefPubMedSearch in Google Scholar
  • 5 Andrew M, Brooker L, Mitchell L. Acquired antithrombin III deficiency secondary to asparaginase therapy in childhood acute lymphoblastic leukaemia. Blood Coagul Fibrinolysis 1994; 5 (Suppl. 01) S24-S36 , discussion S59–S64
    PubMedSearch in Google Scholar
  • 6 Couturier MA, Huguet F, Chevallier P. et al. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: the GRAALL experience. Am J Hematol 2015; 90 (11) 986-991
    CrossrefPubMedSearch in Google Scholar
  • 7 Ranta S, Tuckuviene R, Mäkipernaa A. et al. 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 (04) 547-552
    PubMedSearch in Google Scholar
  • 8 Silverman LB, Gelber RD, Dalton VK. et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001; 97 (05) 1211-1218
    CrossrefPubMedSearch in Google Scholar
  • 9 Arber DA, Orazi A, Hasserjian R. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20) 2391-2405
    CrossrefPubMedSearch in Google Scholar
  • 10 Ferro JM, Bousser MG, Canhão P. et al; European Stroke Organization. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol 2017; 24 (10) 1203-1213
    CrossrefPubMedSearch in Google Scholar
  • 11 Saposnik G, Bushnell C, Coutinho JM. et al; American Heart Association Stroke Council; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular and Stroke Nursing; and Council on Hypertension. Diagnosis and management of cerebral venous thrombosis: a scientific statement from the American Heart Association. Stroke 2024; 55 (03) e77-e90
    CrossrefPubMedSearch in Google Scholar
  • 12 Musgrave KM, van Delft FW, Avery PJ. et al. Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia - a cohort study from the United Kingdom. Br J Haematol 2017; 179 (04) 667-669
    PubMedSearch in Google Scholar
  • 13 Caruso V, Iacoviello L, Di Castelnuovo A. et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 2006; 108 (07) 2216-2222
    CrossrefPubMedSearch in Google Scholar
  • 14 Coutinho JM, Ferro JM, Canhão P. et al. Cerebral venous and sinus thrombosis in women. Stroke 2009; 40 (07) 2356-2361
    CrossrefPubMedSearch in Google Scholar
  • 15 Schaller B, Graf R. Cerebral venous infarction: the pathophysiological concept. Cerebrovasc Dis 2004; 18 (03) 179-188
    CrossrefPubMedSearch in Google Scholar
  • 16 Saposnik G, Barinagarrementeria F, Brown Jr RD. et al; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42 (04) 1158-1192
    CrossrefPubMedSearch in Google Scholar
  • 17 Lauw MN, Van der Holt B, Middeldorp S, Meijers JC, Cornelissen JJ, Biemond BJ. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: effect of fresh frozen plasma supplementation. Thromb Haemost 2013; 109 (04) 633-642
    PubMedSearch in Google Scholar
  • 18 Ghanem KM, Dhayni RM, Al-Aridi C. et al. Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: risk factors and management. Pediatr Blood Cancer 2017; 64 (12) e26694
    PubMedSearch in Google Scholar
  • 19 Lalive PH, de Moerloose P, Lovblad K, Sarasin FP, Mermillod B, Sztajzel R. Is measurement of D-dimer useful in the diagnosis of cerebral venous thrombosis?. Neurology 2003; 61 (08) 1057-1060
    PubMedSearch in Google Scholar
  • 20 Kosinski CM, Mull M, Schwarz M. et al. Do normal D-dimer levels reliably exclude cerebral sinus thrombosis?. Stroke 2004; 35 (12) 2820-2825
    CrossrefPubMedSearch in Google Scholar