Abstract
Asparaginase drugs are integrated to multicomponent chemotherapy protocols for acute lymphoblastic leukemia (ALL) in children and adults. Despite the use of different treatment protocols for ALL therapy, drugs are the same there and the differences include the doses and the frequency of administration of cytostatics. Native L-asparaginase obtained from Escherichia coli was the first asparaginase drug for the treatment of ALL. With accumulated knowledge about undesirable and side effects another asparaginase drugs with less expressed side effects were created: pegylated form (PEG-asparaginase), asparaginase derived from Erwinia chrysanthemi (erwinase) and pegylated form of erwinase (crisantaspase). This review is devoted to modern ideas about the mechanisms of action of various asparaginase drugs, pharmacological properties and adverse effects. There is a particular attention to the development of new forms of asparaginase, which will help minimize side effects and increase the effectiveness of the drug. Of no less importance is drug monitoring of asparaginase in the blood to detect side effect at the time and to understand the effectiveness of the therapy. The introduction of drug monitoring will help to individualize and improve the effectiveness of ALL treatment.
Highlights
Asparaginase drugs are integrated to multicomponent chemotherapy protocols for acute lymphoblastic leukemia (ALL) in children and adults
Native L-asparaginase obtained from Escherichia coli was the first asparaginase drug for the treatment of ALL
With accumulated knowledge about undesirable and side effects another asparaginase drugs with less expressed side effects were created: pegylated form (PEG-asparaginase), asparaginase derived from Erwinia chrysanthemi and pegylated form of erwinase
Summary
Частота тромбозов Frequency of thrombosis Частота панкреатита Frequency of pancreatitis Частота реакции гиперчувствительности Frequency of hypersensitivity Гипергликемия (инсулинотерапия) Hyperglycemia (insulin therapy) Гепатотоксичность Hepatotoxicity. Не менее важный побочный эффект, возникновение которого возможно после введения препаратов L-АСП, – реакция гиперчувствительности, приводящая к резкому снижению активности фермента и отсутствию эффекта от лечения, так как именно истощение запасов L-аспарагина считается важным фактором в достижении оптимальных терапевтических результатов. При развитии реакции гиперчувствительности в фазу индукции ремиссии при ОЛЛ в большинстве случаев антительный ответ опосредован ПЕГ-частью препарата и SS-линкером, в то время как ответ в фазу интенсификации обусловлен выработкой антител преимущественно к ферментной части L-АСП [18, 30, 32,33,34]. Для минимизации рисков развития нежелательных и побочных эффектов после применения препаратов L-АСП рекомендовано проводить лекарственный мониторинг: определять сывороточную концентрацию L-АСП после введения препарата, концентрации аминокислот L-аспарагина и L-глутамина, антител к ферменту и к составляющим частям L-АСП. Variation of native and PEG-asparaginase doses in pediatric ALL BFM protocols
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