Prophylactic Therapy with Enoxaparin in Children with Acute Lymphoblastic Leukemia and Inherited Thrombophilia During L-Asparaginase Treatment.
Authors: Harlev Dan , Zaidman Irina , Sarig Galit , Arush Myriam Ben , Brenner Benjamin , Elhasid Ronit 
Published: October 2019

Abstract 4120

Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL) receiving L-asparaginase in combination with vincristine, prednisone and anthracyclines. They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) is widely used for the prevention of thrombosis in a variety of diseases. Its advantages are prolonged half-life and the low rate of induced thrombocytopenia. To date, there is a debate as to whether or not to give prophylactic treatment for TE using low-dose warfarin or LMWH in children with ALL receiving a combination of L-asparaginase and steroids. In a previous study done by us LMWH was given to all children with ALL during L-asparaginase treatment. In the current study presented herein it was decided to give prophylactic LMWH during L-asparaginase treatment only to patients with ALL and genetic thrombophilia.

Eighty-seven consecutive children with acute onset of ALL treated at Rambam Medical Center between the years 1999 and 2008 were included. Eighty patients were above the age of 1 year and were treated according to the Israeli version of the BFM protocols 1998 and 2002, while seven patients with infant leukemia were treated according to the Interfant-99 protocol. Median age at diagnosis was 4.9 years (range: 0.1-16 years). There were 56 boys and 31 girls. Forty-five patients were Arabic (including Druze), 41 were Jewish and one was Bahai. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1 mg/kg starting with the first dose of L-asparaginase (day 12 during induction, day 8 during consolidation) until one week after the last dose (day 40 during induction, day 25 during consolidation) to patients with inherited thrombophilia; either factor V Leiden or prothrombin mutation.

Twenty (22.9%) patients were found to have a genetic predisposition for TE. Six (6.9%) patients were heterozygous for prothrombin G20210A mutation, while 14 (16%) patients were heterozygous for factor V Leiden mutation. Seven of the 87 (8%) patients developed eight thromboembolic events. Three of these seven were heterozygous for prothrombin mutation and received prophylactic LMWH. The other 4 patients had no genetic thrombophilia and did not receive LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH (Table 1). No bleeding occurred during treatment with LMWH.

It is suggested that prophylactic use of LMWH for prevention of TE events during L-asparaginase treatment is more beneficial to patients harboring factor V Leiden mutation than for those who have prothrombin mutation. A randomized trial of LMWH should be performed in children with ALL during L-asparaginase and steroids treatment, in order to properly asses its safety and efficacy in preventing TE.

Table 1 Number of patients (%) LMWH treatment TE episodes Total number of patients ➞ 7 patients No genetic thrombophilia 67 (77) no 4 Genetic thrombophilia 20 (23) Factor II G20210A 6 Yes 3     Homozygous     Heterozygous 0 Factor V Leiden     Homozygous 14 Yes (in 12 patients) 0     Heterozygous 0 14

Disclosures:

Brenner: sanopi-aventis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.