Download PDF
CC BY 4.0 · Glob Med Genet 2024; 11(03): 214-219
DOI: 10.1055/s-0044-1788043
Case Report

Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy

Shiyuan Wang   *
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Jun Li   *
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Ying Li
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
3   State Key Laboratory of Experimental Hematology, Department of Radiology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
,
Xiaoming Liu
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Lixian Chang
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Beibei Zhao
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Li Zhang
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Yao Zou
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Min Ruan
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
,
Xiaofan Zhu
1   State Key Laboratory of Experimental Hematology, Pediatric Hematology and Oncology Center, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
2   Tianjin Institutes of Health Science, Tianjin, China
› Author Affiliations Funding This work was supported by the CAMS Innovation Fund for Medical Sciences (2022-I2M-1-022), the National Natural Science Foundation of China (82270144).
› Further Information
Also available at
   Permissions and Reprints

Abstract

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Keywords

acute lymphoblastic leukemia - gene mutation - L-Asparaginase - cerebral venous sinus thrombosis

* These authors contributed equally to this work.




Publication History

Article published online:
05 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet 2020; 395 (10230): 1146-1162
    CrossrefPubMedGoogle Scholar
  • 2 Inaba H, Mullighan CG. Pediatric acute lymphoblastic leukemia. Haematologica 2020; 105 (11) 2524-2539
    CrossrefPubMedGoogle Scholar
  • 3 Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021; 71 (01) 7-33
    CrossrefPubMedGoogle Scholar
  • 4 Parsons SK, Skapek SX, Neufeld EJ. et al. Asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia. Blood 1997; 89 (06) 1886-1895
    CrossrefPubMedGoogle Scholar
  • 5 Greiner J, Schrappe M, Claviez A. et al; THROMBOTECT Study Investigators. THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during induction therapy of acute lymphoblastic leukemia in children and adolescents. Haematologica 2019; 104 (04) 756-765
    CrossrefPubMedGoogle 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
    CrossrefPubMedGoogle Scholar
  • 7 Hoogerbrugge N, Jansen H, Hoogerbrugge PM. Transient hyperlipidemia during treatment of ALL with L-asparaginase is related to decreased lipoprotein lipase activity. Leukemia 1997; 11 (08) 1377-1379
    CrossrefPubMedGoogle Scholar
  • 8 Tozuka M, Yamauchi K, Hidaka H, Nakabayashi T, Okumura N, Katsuyama T. Characterization of hypertriglyceridemia induced by L-asparaginase therapy for acute lymphoblastic leukemia and malignant lymphoma. Ann Clin Lab Sci 1997; 27 (05) 351-357
    PubMedGoogle Scholar
  • 9 Kloos RQH, Pieters R, Jumelet FMV, de Groot-Kruseman HA, van den Bos C, van der Sluis IM. Individualized asparaginase dosing in childhood acute lymphoblastic leukemia. J Clin Oncol 2020; 38 (07) 715-724
    CrossrefPubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 Abbott LS, Deevska M, Fernandez CV. et al. The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase. Blood 2009; 114 (25) 5146-5151
    CrossrefPubMedGoogle Scholar
  • 12 Kawabori M, Kuroda S, Kudo K. et al. Susceptibility-weighted magnetic resonance imaging detects impaired cerebral hemodynamics in the superior sagittal sinus thrombosis–case report. Neurol Med Chir (Tokyo) 2009; 49 (06) 248-251
    CrossrefPubMedGoogle Scholar
  • 13 Talamo L, Douvas M, Macik BG, Ornan D. Successful treatment with apixaban of sinus venous thrombosis due to pegylated asparaginase in a young adult with T cell acute lymphoblastic leukemia: case report and review of management. Ann Hematol 2017; 96 (04) 691-693
    CrossrefPubMedGoogle Scholar
  • 14 Sui J, Zhang Y, Yang L. et al. Successful treatment with rivaroxaban of cerebral venous thrombosis and bone marrow necrosis induced by pegaspargase: a case report and literature review. Medicine (Baltimore) 2017; 96 (46) e8715
    CrossrefPubMedGoogle Scholar
  • 15 Parrella A, Iannuzzi A, Annunziata M. et al. Haematological drugs affecting lipid metabolism and vascular health. Biomedicines 2022; 10 (08) 1935
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Athale UH, Chan AK. Thrombosis in children with acute lymphoblastic leukemia Part III. Pathogenesis of thrombosis in children with acute lymphoblastic leukemia: effects of host environment. Thromb Res 2003; 111 (06) 321-327
    PubMedGoogle Scholar
  • 18 Rank CU, Toft N, Tuckuviene R. et al. Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood 2018; 131 (22) 2475-2484
    CrossrefPubMedGoogle Scholar
  • 19 Gupta S, Wang C, Raetz EA. et al. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. J Clin Oncol 2020; 38 (17) 1897-1905
    CrossrefPubMedGoogle Scholar