OC 32.3 - Low-molecular-weight heparin for the prevention of venous thromboembolism in adults with newly diagnosed acute lymphoblastic leukemia; prospective side-study of the HOVON-100 trial

Monday, June 24, 2024

10:00 – 10:15 ICT

Room: Ballroom B2

Presenting Author(s)

Mandy N. Lauw, MD PhD

Internist-hematologist
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

AR

Anita W. Rijneveld

Internist-hematologist
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Amica K. Ko, MD MSc

MD, PhD Candidate
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
BV

Bronno Van der Holt

Statistician
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
CF

Cathelijne A. Fokkema

MD, PhD Candidate
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Saskia Middeldorp, MD, PhD

Internist, Professor
Radboud university medical center
Nijmegen, Gelderland, Netherlands
Frank W.G Leebeek, MD PhD

Internist-hematologist, Professor
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
BB

Bart J. Biemond

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

Background: Adults with acute lymphoblastic leukemia/lymphoma (ALL) have a 10-40% risk of venous thromboembolism (VTE), leading to morbidity and decreased survival. Optimal preventive management is currently unclear.

Aims: We investigated whether primary thromboprophylaxis using low-molecular-weight heparin (LMWH) during ALL remission-induction treatment could prevent thrombosis.

Methods: We performed a prospective side-study in the HOVON-100 trial for adults aged 18-70 years with newly diagnosed ALL (2009-2016; Rijneveld, Blood Adv 2022). Starting January 2012, all patients received fixed intermediate-dose LMWH (nadroparin 5700 anti-Xa IU) from the start of ALL-treatment (prephase) until day 35 of remission-induction cycle1 (RI1). RI1 included two PEG-Asparaginase administrations for patients aged 18-40 years (day8,day21) but no PEG-asparaginase for patients 41-70 years. All symptomatic thrombosis and bleeding events were collected. Primary outcome was venous or arterial thrombosis after the first 60 days of ALL-treatment, secondary outcomes were overall thrombosis and major bleeding.

Results: 369 of 370 adults included in HOVON-100 were used for this analysis. 253 patients received LMWH and 116 did not (Table 1). After the first 60 days of ALL-treatment, 57/369 (15%) patients experienced thrombosis (56 venous, 1 arterial; Table 2). LMWH did not prevent thrombosis during these first 60 days (44/253 (17%) patients with LMWH, versus 13/116 (11%) patients without thromboprophylaxis; adjusted subdistribution hazard ratio [SHR] 1.52; 95% CI 0.79-2.90), with an age-dependent disparity (18-40 years: SHR 0.88; 95%CI 0.37-2.08; 41-70 years: SHR 2.47; 95%CI 0.92-6.63). No difference was found in bleeding after prephase and RI1 (7% with LMWH, 3% without).

Conclusion(s): Thrombosis incidence was 15% after the first 60 days of ALL-treatment. LMWH in fixed intermediate-dose for 35 days did not prevent thrombosis. Indeed, LMWH may even be disadvantageous for older patients not receiving PEG-Asparaginase. This is the largest prospective comparative-cohort study on thromboprophylaxis using LMWH in adults with ALL, confirming the high thrombosis risk. Randomized trials are needed for confirmation.