Anticoagulation Prophylaxis With Enoxaparin For Patients With Acute Lymphoblastic Leukemia Receiving Asparaginase-Based Intensification Therapy

Venous thromboembolism (VTE) is a well-known complication in patients treated with asparaginase-containing regimens; the optimal preventative strategy is unclear. We assessed the safety and efficacy of low-dose low molecular weight heparin (LMWH) prophylaxis in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) treated with an asparaginase- based regimen.

Patients were treated with the DFCI 91-01 protocol from 2009-2012; patients age 60 and over received a modified version. All patients who were in complete remission and received at least 7 cycles (21 weeks) of the asparaginase-based intensification phase were evaluable for analysis. Patients already on anticoagulation for prior VTE were excluded. Patients received enoxaparin subcutaneously once daily, at a dose of 40 mg for patients weighing less than 80 kg and 60 mg for those 80 kg and over, beginning on day 1, cycle 1 of intensification until the completion of the entire 21-30 week intensification phase. Results were compared to a similar cohort of consecutive patients treated with the same protocol prior to 2009, without anticoagulation prophylaxis.

There were 41 evaluable patients who received enoxaparin prophylaxis. The historical cohort (n=99) did not significantly differ from this group with respect to median age, weight and number of treatment cycles per patient. The mean enoxaparin dose administered was 0.62 mg/kg (range 0.39-1.05 mg/kg). As shown in Table 1, the overall rate of VTE was not significantly different than the historical non-prophylaxed cohort. Among patients receiving prophylaxis, there was a higher rate of VTE in patients who weight at least 80 kg, despite the higher enoxaparin dose used (p=0.036). There was no significant difference in the rate of VTE according to age or gender. Sites of VTE in the prophylaxed group included lower extremity (8 cases), sagittal sinus (2), subclavian line related (2), and pulmonary embolism (6). There were no major bleeding complications observed in the prophylaxed group (minor bleeding 3/41).

Prophylaxis with low-dose enoxarain during the intensification phase was safe, but did not show a significant benefit in reducing the rate of VTE. Prospective randomized studies are needed, using more intensive or novel prophylaxis strategies, in adult ALL patients treated with asparaginase-containing regimens.

Off Label Use: enoxaparin for VTE prophylaxis in ALL.