Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia.
BACKGROUND
The concentrations of plasma hemostatic proteins were analyzed prospectively in 42 children with acute lymphoblastic leukemia (ALL), treated according to the protocol ALL-BFM-90.


METHODS
Treatment included glucocorticosteroids (GC), E. coli L-asparaginase (Asparaginase, Medac) or Erwinia L-asparaginase (Erwinase, Speywood), vincristine, anthracyclines and intrathecal methotrexate. The analysis of hemostatic proteins was performed during induction and re-induction therapy.


RESULTS
At diagnosis, the plasma concentrations of fibrinogen, antithrombin III (AT), plasminogen and protein C were within normal limits, whereas the von Willebrand factor antigen (vWF:Ag) was elevated. After eight days of mono-therapy with GC the concentration of fibrinogen decreased to 59%, vWF:Ag decreased to 67%, AT increased to 124%, protein C increased to 201% of the initial value (mean all p < or = 0.01), while the concentration of plasminogen remained unchanged. During the re-induction phase, the concentrations of the hemostatic proteins, with exception of vWF:Ag, altered in a similar way in response to GC as observed during the induction phase. Administration of two doses of E. coli L-asparaginase (10,000 U/m2) during the induction therapy led to a significant decrease of AT (123 +/- 24 to 63 +/- 15%/mL), protein C (168 +/- 34 to 87 +/- 19%/mL), plasminogen (94 +/- 21 to 41 +/- 12%/mL) and fibrinogen (148 +/- 59 to 79 +/- 30 mg/dL, p < or = 0.01 for all parameters). In contrast, administration of two doses of Erwinia L-asparaginase (10,000 U/m2) during re-induction therapy did not lead to change in the concentration of AT, protein C or plasminogen, and the decrease in fibrinogen (162 +/- 17 to 121 +/- 24 mg/dL) was less pronounced.


CONCLUSIONS
Our results indicate that GC and E. coli L-asparaginase, in particular, induce hemostatic alterations which have implications on our understanding of thrombotic and hemorrhagic events during the treatment of ALL in children.
Mall
V
V
Universitäts-Kinderklinik, Freiburg, Germany.
Thomas
K B
KB
Sauter
S
S
Niemeyer
C M
CM
Sutor
A H
AH
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001215:Asparaginase / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004885:Erwinia / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies; D012074:Remission Induction
D001779:Blood Coagulation Factors; D005938:Glucocorticoids; D001215:Asparaginase