An antithrombin replacement strategy during asparaginase therapy for acute lymphoblastic leukemia is associated with a reduction in thrombotic events

Leuk Lymphoma. 2016 Nov;57(11):2568-74. doi: 10.3109/10428194.2016.1165815. Epub 2016 Apr 14.

Abstract

Thrombosis is a well-recognized complication of asparaginase therapy for acute lymphoblastic leukemia (ALL), associated with the depletion of antithrombin (AT). Following a high incidence of thrombotic episodes during induction therapy for ALL in our tertiary referral center, we prospectively instituted a protocol of AT replacement. Forty-five consecutive adolescents and adults with ALL treated with asparaginase-containing phase I induction protocols were included in this observational study. Fifteen received standard therapy with no replacement; the subsequent 30 were managed with the protocol described. One or more low AT levels (<70 iu/dl) were recorded in 76% of patients in the cohort managed using the protocol, resulting them in receiving an AT replacement. There was a significant reduction in the incidence of thrombosis with this strategy (0/30 vs. 5/15, p < 0.001). We suggest that such a strategy should be studied in a prospective randomized sub-study within the context of a national ALL trial.

Keywords: Acute lymphoblastic leukemia; antithrombin; asparaginase; thrombosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antithrombins / therapeutic use*
  • Asparaginase / adverse effects*
  • Asparaginase / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Retrospective Studies
  • Thrombosis / drug therapy*
  • Thrombosis / etiology*
  • Thrombosis / prevention & control
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Antithrombins
  • Asparaginase