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.
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.


METHODS
This was a retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m(2) 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.
Hunault-Berger
Mathilde
M
Hematology Department of Angers, France.
Chevallier
Patrice
P
Delain
Martine
M
Bulabois
Claude-Eric
CE
Bologna
Serge
S
Bernard
Marc
M
Lafon
Ingrid
I
Cornillon
Jérome
J
Maakaroun
Abdallah
A
Tizon
Alexandra
A
Padrazzi
Bruno
B
Ifrah
Norbert
N
Gruel
Yves
Y
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000991:Antithrombins / Q000378:metabolism*; D001215:Asparaginase / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D015996:Survival Rate; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000991:Antithrombins; D005340:Fibrinogen; D001215:Asparaginase