The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols

Br J Haematol. 2011 Feb;152(4):452-9. doi: 10.1111/j.1365-2141.2010.08524.x. Epub 2011 Jan 7.

Abstract

The optimal management of asparaginase-associated thrombotic complications is not well-defined. We report the features, management and outcome of paediatric (ages 0-18years) and adult (18-50years) patients with acute lymphoblastic leukaemia (ALL) with asparaginase-related venous thromboembolic events (VTE) treated at Dana-Farber Cancer Institute on clinical trials for newly diagnosed ALL between 1991-2008. Of 548 patients, 43 (8%) had VTE, including 27/501 (5%) paediatric and 16/47 (34%) adult patients. Sinus venous thrombosis occurred in 1·6% of patients. Age was the only significant predictor of VTE, with those aged >30years at very high risk (VTE rate 42%). 74% of patients received low molecular weight heparin after VTE. Complications of anticoagulation included epistaxis (9%), bruising (2%) and, in two adult patients, major bleeding. Thirty patients (70%) ultimately received at least 85% of the intended doses of asparaginase. 33% of patients experienced recurrent VTE (paediatric 17% vs. adults 47%, P=0·07). The 48-month event-free survival for patients with VTE was 85±6% compared with 88±2% for those without VTE (P=0·36). This study confirms that, after VTE, asparaginase can be restarted with closely monitored anticoagulation after imaging demonstrates clot stabilization or improvement. With this management strategy, a history of VTE does not appear to adversely impact prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Age Factors
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Asparaginase / administration & dosage
  • Asparaginase / adverse effects*
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Drug Administration Schedule
  • Epidemiologic Methods
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prognosis
  • Recurrence
  • Treatment Outcome
  • Venous Thromboembolism / chemically induced*
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / therapy
  • Young Adult

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Asparaginase