Pegaspargase in clinical practice: a literature review and toxicity analysis after 1.5 years of its use in patients with acute lymphoblastic leukemia treated at an oncology/hematology department

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Abstract

Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of hematological malignancies accounting for approximately 25% of all cancer cases in children under 15 years of age. Over the past 40 years, the treatment of ALL in children has improved drastically due to the development and continuous improvement of risk stratification and incorporation of multiagent chemotherapy protocols including central nervous system prophylaxis. Asparaginase has played a major role in the improvement of ALL treatment outcomes in children and has been a critical part of ALL management since 1960s. L-asparaginase derived from Escherichia coli and Erwinia chrysanthemi is an enzyme causing depletion of serum asparagine which leads to its deprivation and consequent inhibition of protein synthesis, and hence limited survival of lymphoblasts that are known to be highly dependent on exogenous asparagine. Pegaspargase, a conjugate of methoxypolyethylene glycol and L-asparaginase, has become an integral part of treatment protocols for primary and relapsed ALL due to its longer half-life and an improved immunogenicity profile compared to native asparaginase medicines. However, the use of pegaspargase is associated with various toxicity and side effects that are observed in 25–30% of patients, with hypersensitivity being the most common reaction. Other toxicities include asparaginase-associated pancreatitis, thrombosis/bleeding, liver dysfunction, osteonecrosis, and dyslipidemia. Failure to receive the entire course of asparaginase therapy is associated with poorer treatment outcomes. The awareness and rapid identification of asparaginase-associated toxicity ensure effective toxicity prevention and treatment and help achieve maximum benefit from asparaginase therapy. Here, we offer an overview of the most common toxicities associated with pegaspargase treatment based both on literature data and on the results of our analysis of the drug’s clinical use at a Russian pediatric oncology/hematology department. The study was approved by the Independent Ethics Committee of the Children’s Multi-Specialty Clinical Center of High Medical Technologies.

About the authors

E. G. Boychenko

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Email: boychenko-elmira@yandex.ru
ORCID iD: 0000-0002-2731-4531

Elmira G. Boychenko - Dr. Med. Sci., Head of the Department of Oncology/hematology at Children’s Multi-Specialty Clinical Center of High Medical Technologies, Chief External Expert in Pediatric Hematology of Saint Petersburg Healthcare Committee.

14A Avangardnaya St., 198205 Saint-Petersburg

Russian Federation

A. R. Islamova

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Email: alsushka99@bk.ru
ORCID iD: 0009-0003-2794-5514

Saint-Petersburg

Russian Federation

D. Kh. Senova

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Author for correspondence.
Email: disanasenova@mail.ru
ORCID iD: 0009-0006-8127-3159

Saint-Petersburg

Russian Federation

I. A. Garbuzova

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

M. A. Prudnikova

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

N. А. Filatova

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

E. E. Usmanskaya

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

N. N. Ivanov

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

A. A. Gogun

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

K. I. Pshenichnaya

Children’s Multi-Specialty Clinical Center of High Medical Technologies

Saint-Petersburg

Russian Federation

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Copyright (c) 2025 Boychenko E.G., Islamova A.R., Senova D.K., Garbuzova I.A., Prudnikova M.A., Filatova N.А., Usmanskaya E.E., Ivanov N.N., Gogun A.A., Pshenichnaya K.I.

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