Clinical Course of Cerebral Venous Thrombosis in Adult Acute Lymphoblastic Leukemia

J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1679-84. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.041. Epub 2015 Apr 29.

Abstract

Background: Venous thromboembolism (VTE) is a frequent complication in patients with acute lymphoblastic leukemia (ALL). A significant proportion of patients develop cerebral venous thrombosis (CVT).

Methods: To investigate risk factors for and the clinical course of CVT in ALL patients, we describe all cases of CVT which occurred in a well-defined cohort of 240 adults, treated for newly diagnosed ALL in the HOVON (Dutch-Belgian Hemato-Oncology Cooperative Group)-37 study. We conducted a nested case-control study to explore the relevance of early symptoms and risk factors for CVT in ALL patients.

Results: Nine of 240 patients developed CVT (4%). CVT occurred during or shortly after L-asparaginase therapy (in 8 cases) and shortly after intrathecal methotrexate injections (in all cases) during cycle I of remission induction treatment. CVT was associated with prior headache and seizures. In 5 of 9 patients with CVT, headache before the diagnosis of CVT occurred within 3 days after lumbar puncture and initially had a postural character.

Conclusions: CVT is relatively common in adult ALL patients. Our data suggest that CVT in adult ALL patients results from the additive effects of multiple risk factors, with a particular role for asparaginase and the effects of lumbar punctures for intrathecal therapy.

Keywords: Cerebral venous thrombosis; L-asparaginase; acute lymphoblastic leukemia; chemotherapy; risk factor; venous thrombosis.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Asparaginase / administration & dosage
  • Asparaginase / adverse effects*
  • Cerebrovascular Disorders / diagnosis
  • Cerebrovascular Disorders / etiology*
  • Clinical Trials, Phase II as Topic
  • Drug Administration Schedule
  • Female
  • Headache / etiology
  • Humans
  • Injections, Spinal
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Middle Aged
  • Netherlands
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • Seizures / etiology
  • Spinal Puncture / adverse effects*
  • Time Factors
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / etiology*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / etiology*
  • Young Adult

Substances

  • Asparaginase
  • Methotrexate

Associated data

  • NTR/NTR228