ABSTRACT

This chapter shows that patients with a hypersensitivity reaction toward Escherichia coli-Asp had significantly elevated IgG and IgM antibody levels toward E. coli-Asp. It argues that the combination of steroids and l-asparaginase (l-Asp) early in the induction treatment might be a potent prothrombotic risk factor, especially in patients with genetic prothrombotic risk factors. The chapter suggests that the risk of thrombosis was significantly higher if l-Asp was combined with prednisone compared with a combination of l-Asp and dexamethasone. In the 1990s, l-Asp derived from E. coli or Erwinia chrysanthemi was used in treatment protocols in equal doses and schedules, as if these substances were one and the same drug. Besides unmodified l-Asp preparations, chemically modified forms were introduced in order to reduce the immunogenicity of the enzyme, as this is one of the limiting factors in clinical use. The enzyme has been coupled to polyethylene glycol, dextran, or poly-dl-alanyl peptides.