A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase

Results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study

Authors

  • Lesley G. Mitchell M.Sc.,

    Corresponding author
    1. Population Health Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
    • Population Health Sciences, Hospital For Sick Children, 555 University Avenue, Toronto, Ontario, Canada. M5G 1X8
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    • Fax: (416) 813-5979

    • L.G.M. is a research scholar of the Canadian Institutes of Health Research. M.A. and J.G. are a career investigators of the Heart and Stroke Foundation of Ontario.

  • and the PARKAA Group

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    • Members of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) group are: Maureen Andrew MD, Population Health Sciences, The Hospital for Sick Children, Toronto, Canada; Kim Hanna M Sc, Bayer Inc., Toronto, Canada; Thomas Abshire MD, Hematology/Oncology, Emory University School of Medicine, Atlanta, USA; Jacqueline Halton MD, Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, Canada; Ron Anderson MD, Dept Hematology/Oncolcogy, Alberta Children's Hospital, Calgary, Canada; Irene Cherrick MD, Dept Hematology/Oncology, University Hospital, Syracuse, USA; Sunil Desai MD, Dept Hematology/Oncology, W MacKenzie Health Sciences Centre, Edmonton, Canada; Donald Mahoney MD, Dept Hematology/Oncology, Texas Children's Hospital, Houston, USA; Patricia McCusker MD, Hematology/Oncology, Children's Hospital of Western, London, Canada; John Wu MD, Hematology/Oncology, B.C. Children's Hospital, Vancouver, Canada; Gary Dahl MD, Hematology/Oncology, Stanford University School of Medicine, Palo Alto, USA; Peter Chait MD, Radiology, Hospital for Sick Children, Toronto, Canada; Gabrielle de Veber, Neurology, Hospital for Sick Children, Toronto, Canada; Kyong-Jin Lee MD, Cardiology, Hospital for Sick Children, Toronto, Canada; David Mikulis, Neurology, Toronto General Hospital, Toronto, Canada; Jeffrey Ginsberg MD, Medicine, McMaster University, Hamilton, Canada; Clifford Way MD, Cardiology, McMaster University, Hamilton, Canada.


  • The authors are all deeply saddened by the loss of their colleague and friend, Dr. Maureen Andrew, who passed away suddenly on August 28, 2001. Dr. Andrew was instrumental in the work reported here, and the authors respectfully dedicate this article to her memory.

Abstract

BACKGROUND

Thrombotic events (TEs) are serious secondary complications in children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP) therapy; however, the prevalence of TEs has not been established. The primary objective of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine the prevalence of TEs. The secondary objective was to detect any association of TEs with the presence of congenital or acquired prothrombotic disorders.

METHODS

Children with ALL were screened for TEs at the end of ASP treatment using bilateral venograms, ultrasound, magnetic resonance imaging, and echocardiography. Symptomatic TEs were confirmed by appropriate radiographic tests. All tests were read by a blinded central adjudication committee.

RESULTS

Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence interval, 24.4–48.8%). TEs were located in the sinovenous system of the brain in 1 patient, the right atrium in 3 patients, and the upper central venous system in 19 patients. TEs detected by venography resulted in 1) 25–100% occlusion, with 1 in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2) the presence of collaterals in 60% of patients, with 40% categorized as major. No children with TEs were positive for factor V Leiden or prothrombin gene 20201A, and four of eight children with antiphospholipid antibodies had a TE.

CONCLUSIONS

The prevalence of TEs is exceedingly high in this population, and it is likely that the extent of occlusion is likely clinically significant. No trend was seen toward an association between TEs and the presence of congenital prothrombotic disorders. A trend was seen toward an association between TEs and antiphospholipid antibodies. Carefully designed clinical trials of primary prophylaxis for the prevention of TEs are required in this patient population. Cancer 2003;97:508–16. © 2003 American Cancer Society.

DOI 10.1002/cncr.11042

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