Published online 25 August 2008
Haematologica, Vol 93, Issue 10, 1488-1494 doi:10.3324/haematol.12948
Copyright © 2008 by Ferrata Storti Foundation

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Acute Lymphoblastic Leukemia

Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study

Mathilde Hunault-Berger¹, Patrice Chevallier², Martine Delain³, Claude-Eric Bulabois⁴, Serge Bologna⁵, Marc Bernard⁶, Ingrid Lafon⁷, Jérome Cornillon⁸, Abdallah Maakaroun³, Alexandra Tizon¹, Bruno Padrazzi⁹, Norbert Ifrah¹, Yves Gruel³ for the GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang)

¹ Hematology Departments of Angers
² Nantes
³ Tours
⁴ Grenoble
⁵ Nancy
⁶ Rennes
⁷ Dijon
⁸ Saint Etienne
⁹ LFB-Paris, France

Correspondence: Yves Gruel, Service d’Hématologie Hémostase, Hôpital Trousseau, 37044 Tours Cedex, France. E-mail:gruel{at}med.univ-tours.fr

Background: The effects of L-asparaginase on hemostasis during induction chemotherapy are less defined in adults than in children. We, therefore, studied the effects of L-asparaginase in adult patients.

Design and Methods: This was a retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m² x 6) for acute lymphoblastic leukemia or lymphoblastic lymphoma. Between day 1 of the induction course and discharge, clinical events, and biological and therapeutic modifications were reviewed.

Results: Antithrombin and fibrinogen levels were lower than 60% and 1 g/L in 71% and 73% of patients, respectively. Twenty thromboses occurred in 9.3% of the patients; these patients had a median antithrombin level of 53% (range, 21–111) at the time of the event. Forty-two episodes of bleeding occurred in 31 patients with a median fibrinogen level of 1.3 g/L. Infusions of L-asparaginase were reduced or delayed in 64% of patients due to low fibrinogen and/or antithrombin levels. Fresh-frozen plasma, antithrombin and fibrinogen were infused in 31%, 41% and 52% of patients, respectively. The mean antithrombin and fibrinogen levels increased from 61% to 88% and from 1 to 1.4 g/L after infusion of antithrombin or fibrinogen respectively, while both levels remained unchanged after the infusion of fresh-frozen plasma. In patients who received antithrombin concentrates L-asparaginase injections were less frequently omitted or delayed (53% vs. 72%, p=0.005), the rate of thrombosis was lower (4.8% vs. 12.2%, p=0.04) and the disease-free survival was also reduced (p=0.05).

Conclusions: This retrospective study suggests that antithrombin concentrates may have a beneficial effect on the outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase; prospective studies are essential to confirm this hypothesis.

Key words: L-asparaginase, acute lymphoblastic leukemia, antithrombin, fibrinogen.

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