Feasibility and safety of delivering full-dose anticoagulation therapy in children treated according to Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols

Pediatr Blood Cancer. 2019 Feb;66(2):e27483. doi: 10.1002/pbc.27483. Epub 2018 Oct 25.

Abstract

Background: The literature is void of an evidence-based anticoagulation therapy (ACT) management strategy in the context of thrombocytopenia. We examined the impact of thrombocytopenia on low-molecular-weight heparin (LMWH) dosing and incidence of bleeding in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) who developed thromboembolism (TE) during therapy according to DFCI ALL protocols.

Procedure: Patient records from our tertiary care center were reviewed for demographics, details of diagnoses and therapy of ALL/LL and TE diagnoses, platelet counts during ACT, LMWH dosing, and bleeding episodes.

Results: Thirty-nine TEs were diagnosed in 33 patients [mean age 9 years (range, 2.5-18); 16 males and 31 with ALL] during the study period. A majority (85%) of patients were diagnosed with TE in the consolidation phase with mean time to TE 5.75 months from ALL/LL diagnosis. All patients received LMWH, and the median duration of ACT was 5.9 months (range, 1-11 months). Platelets were measured weekly. On 29 occasions, platelet nadir was <50 × 109 /L, and twice it was < 20 × 109 /L. One (3%) patient had major bleeding episode while on ACT. Platelet count at the time of bleeding was 222 × 109 /L. Ninety-two procedures [83 lumbar punctures (LPs), 9 central venous line (CVL) insertion/revision] were completed without bleeding complications. Asparaginase was held temporarily with TE diagnosis in 48% of patients; most (88%) patients completed all scheduled doses as per protocol.

Conclusions: Ability to administer full-dose LMWH, expected bleeding rate, and completion of asparaginase doses while on ACT suggest full-dose ACT is feasible and safe in children with ALL/LL who develop TE during DFCI ALL consortium therapy protocols.

Keywords: acute lymphoblastic leukemia; anticoagulation therapy; low-molecular-weight heparin; thrombocytopenia; thromboembolism.

MeSH terms

  • Adolescent
  • Anticoagulants / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Child
  • Child, Preschool
  • Cohort Studies
  • Feasibility Studies
  • Female
  • Hemorrhage / epidemiology
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Humans
  • Incidence
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Retrospective Studies
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / complications*
  • Thromboembolism / chemically induced
  • Thromboembolism / drug therapy*

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Heparin, Low-Molecular-Weight