PB0939 - Effect of pegylated asparaginase on coagulation parameters and thrombin generation in adults with acute lymphoblastic leukemia

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Amica K. Ko, MD MSc

MD/PhD Candidate
Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

MT

Max B. Tijssen

Research Technician
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Moniek P.M. de Maat, PhD

Professor
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Joost C.M Meijers, PhD (he/him/his)

Professor
Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Saskia Middeldorp, MD PhD

Professor
Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
BB

Bart J. Biemond

Professor
Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
AR

Anita W. Rijneveld

Hematologist
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Mandy N. Lauw, MD PhD

Internist-Hematologist
Erasmus MC, Rotterdam, Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Intensification of asparaginase treatment in pediatric-inspired chemotherapy regimens for adults with acute lymphoblastic leukemia (ALL) has improved survival, but also increased venous thromboembolism (VTE) risk with incidences reported up to 30%. The pathogenesis of VTE in ALL remains poorly understood, especially in adults due to scarce data.

Aims: To compare coagulation parameters and thrombin generation over time in adults treated for ALL with and without pegylated asparaginase (PEGAsp) during the first remission-induction cycle (RI1), and to evaluate potential associations with VTE.

Methods: 340 adults with newly diagnosed ALL were included in the HOVON-100 trial (Rijneveld et al, 2022). Patients ≤40 years received PEGAsp on day 8 and 21 in RI1, whereas patients >40 years received no PEGAsp. We collected consecutive plasma samples at baseline and every 7 days during RI1. Antithrombin, fibrinogen, D-dimer and FVIII were assessed using Sysmex CS-5100. Thrombin generation was measured by calibrated automated thrombography. Median and IQR values were calculated per parameter for each age group.

Results: Symptomatic VTE occurred in 113/340 (33%) HOVON-100 patients. We collected samples of 99 patients from 12 Dutch centers; 40 of 99 patients (40%; 25/40 ≤40 years, 15/40 >40 years) experienced VTE during ALL treatment, including 13 in RI1. Antithrombin was clearly reduced in patients ≤40 years treated with PEGAsp compared to those >40 years without PEGAsp (Fig. 1). Fibrinogen, D-dimer and FVIII levels did not differ between groups. In all patients, thrombin generation (i.e. endogenous thrombin potential (ETP)) was higher at baseline compared to normal pooled plasma. ETP further increased in patients with PEGAsp, particularly during antithrombin levels nadir (Fig. 2). No association was observed between antithrombin, thrombin generation and VTE, possibly because of insufficient power.

Conclusion(s): Antithrombin reduction and increased thrombin generation were observed in adults with ALL during RI1, particularly in patients treated with PEGAsp. No association with VTE was found.