Changes in coagulation and fibrinolysis in childhood acute lymphoblastic leukaemia re-induction therapy using three different asparaginase preparations

Recently we reported the influence of two different Escherichia coli asparaginase (ASP) preparations on fibrinolytic proteins in childhood acute lymphoblastic leukaemia (ALL) demonstrating a significant association between ASP activity and haemostatic alterations. The present study was designed for prospective evaluation of coagulation and fibrinolytic parameters in leukaemic children receiving different ASP preparations during the course of re-induction. Forty leukaemic children receiving ASP (Medac: n=13; Bayer: n = 10; Erwinia: n = 17) at 3-day intervals during re-induction were enrolled in this study. Blood samples for coagulation studies were obtained before each ASP administration together 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 plasminogen showed normal values in children after Erwinia ASP. alpha 2-antiplasmin and D-Dimer were no different in the groups studied. Neither side-effects, nor sustained asparagine depletion was observed in the majority of children treated with Erwinia ASP. Conclusion Data of this study show a down-regulation of coagulation proteins in children treated with Medac ASP, less pronounced in patients after Bayer or Erwinia ASP. Since children treated with Erwinia ASP showed no adequate asparagine depletion during the course of ASP therapy, a dose adjustment should be discussed to guarantee asparagine depletion, the specific metabolic therapy for ALL.