Prophylactic therapy with enoxaparin during l-asparaginase treatment in children with acute lymphoblastic leukemia

Abstract

Forty-one consecutive children with acute lymphoblastic leukemia (ALL) received prophylaxis therapy with the low molecular weight heparin (LMWH) enoxaparin during L-asparaginase treatment. Enoxaparin was given every 24 h subcutaneously at a median dose of 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) starting at the first dose of L-asparaginase until 1 week after the last dose. Molecular analysis for thrombophilic polymorphisms documented prothrombin G20210A mutation in 3/27 (11%), homozygosity for MTHFR C677T mutation in 5/27 (18.5%, and heterozygosity for factor V Leiden mutation in 5/27 (18.5%) children. There were no thrombotic events during 76 courses of L-asparaginase in 41 patients who had received enoxaparin. One patient suffered brain infarct 7 days after enoxaparin was stopped. There were no bleeding episodes. In a historical control group of 50 ALL children who had not received prophylactic enoxaparin during L-asparaginase treatment, two had thromboembolisms (one deep vein thrombosis and one pulmonary embolism). Enoxaparin is safe and seems to be effective in prevention of thromboembolism in ALL patients during L-asparaginase therapy. This study provides pilot data for a future randomized trial of the use of LMWH during ALL therapy for the prevention of asparaginase-associated thrombotic events.

Venous Thromboembolism Prevention During Asparaginase-Based Therapy for Acute Lymphoblastic Leukemia

“…However, the safety of those agents in such patients is unknown, and there are potential issues with the newer agents concerning drug interactions and difficulties in reversing bleeding. Antithrombin iii concentrates have been used effectively in the induction setting 15 ; however, its routine use in a prolonged intensification phase would be impractical.…”

“…Few data have been reported about the prevention of vte in such patients. A study in pediatric all patients treated with an asparaginase-containing regimen demonstrated that the use of low-molecular weight heparin (lmwh) prophylaxis was associated with a low risk of vte 15 ; however, the control group in that study had only a 4% vte rate. A prospective nonrandomized study in children with all, comparing antithrombin alone with antithrombin plus lmwh, found that prophylaxis with enoxaparin was associated with a lower proportion of vte (12.7% vs. 0%, p = 0.02), without an increase in bleeding complications 16 .…”

L-Asparaginase and Venous Thromboembolism in Acute Lymphocytic Leukemia

“…Although this study demonstrated no clear evidence of the reduced levels of these proteins in identifying at-risk patients, this may have been related to small sample size. An Israeli pediatric study (n = 41) utilizing enoxaparin prophylaxis (discussed later in detail) demonstrated a high incidence of genetic thrombophilia in 27 children (11% prothrombin G20210A and 18% factor V Leiden), who were Arabs and Jews in ethnic origin; however, no one had any VTE [31].…”

The coagulopathy and thrombotic risk associated with L-Asparaginase treatment in adults with acute lymphoblastic leukaemia

“…A nonrandomised study of 41 paediatric patients with ALL using the low molecular weight heparin (LMWH) enoxaparin as prophylaxis during L-Asp therapy reported no thrombotic events during 76 courses of L-Asp, with 1 brain infarct reported 7 days after cessation of prophylaxis. 66 LMWH has also been used successfully as secondary prophylaxis in patients re-exposed to L-Asp following an initial VTE without recurrence or excess bleeding. 67 However, there remains concern that heparins, which rely on AT for their mechanism of action, may not be the most appropriate option.…”