CHANGES IN COAGULATION AND FIBRINOLYSIS IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA RE-INDUCTION THERAPY USING 3 DIFFERENT ASPARAGINASE PREPARATIONS

Recently we reported the influence of two different Escherichia coli a sparaginase (ASP) preparations on fibrinolytic proteins in childhood a cute lymphoblastic leukaemia (ALL) demonstrating a significant associa tion between ASP activity and haemostatic alterations. The present stu dy was designed for prospective evaluation of coagulation and fibrinol ytic parameters in leukaemic children receiving different ASP preparat ions during the course of re-induction. Forty leukaemic children recei ving ASP (Medac: n=13; Bayer: n = 10; Erwinia: n = 17) at 3-day interv als during re-induction were enrolled in this study. Blood samples for coagulation studies were obtained before each ASP administration toge ther with serum samples for pharmacokinetic monitoring. Compared with Medac ASP 10,000 IU/m(2), patients receiving Bayer ASP or Erwinia ASP showed significantly higher fibrinogen values. Antithrombin and plasmi nogen showed normal values in children after Erwinia ASP. alpha 2-anti plasmin and D-Dimer were no different in the groups studied. Neither s ide-effects, nor sustained asparagine depletion was observed in the ma jority of children treated with Erwinia ASP. Conclusion Data of this s tudy show a down-regulation of coagulation proteins in children treate d with Medac ASP, less pronounced in patients after Bayer or Erwinia A SP. Since children treated with Erwinia ASP showed no adequate asparag ine depletion during the course of ASP therapy, a dose adjustment shou ld be discussed to guarantee asparagine depletion, the specific metabo lic therapy for ALL.