Pegaspargase in pediatric acute lymphoblastic leukemia

Cynthia Bender, 1 Luke Maese, 2 Maria Carter-Febres, 2 Anupam Verma 2

1 Department of Pharmacy, Primary Children’s Hospital, Salt Lake City, UT, USA; 2 Department of Hematology / Oncology, Department of Pediatrics, University of Utah and Primary Children’s Hospital, Salt Lake City, UT, USA

Correspondence: Anupam Verma
Pediatric Hematology / Oncology, University of Utah, Primary Children’s Hospital, 100 N Mario Capecchi Drive, Salt Lake City, UT, 84113, USA
Tel. +1 801 662 4700
Fax +1 801 662 4707
E-mail [email protected]

Abstract: Acute lymphoblastic leukemia (ALL) is a heterogeneous haematological malignancy representing 25% of all cancers in children under 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatments. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi, have become an essential part of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this crucial amino acid for protein synthesis, thus limiting lymphoblast survival. Pegaspargase, a conjugate of monomethoxy polyethylene glycol (mPEG) and L-asparaginase, has become an integral part of pediatric initial and recurrent ALL protocols due to its longer half-life and improved immunogenicity profile compared to natural asparaginase preparations. Great strides have been made in the outcomes for ALL in children over the past two decades as a result of risk stratification, inclusion of multi-agent chemotherapy protocols and central nervous system prophylaxis with pegaspargase playing an important role in this success. However, adolescents and young adults (AYA) with ALL treated in concurrent studies of adult ALL regimens continue to have poor results. There is an increasing realization of adapting pediatric trial regimens for the treatment of AYAs, especially those with higher intensity chemotherapeutic agents, pegaspargase being such an agent. Dose- or treatment-limiting toxicity is observed in 25-30% of patients, the most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis and dyslipidaemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival, leading to a higher risk of relapse, and in cases of relapse, a higher risk of remission failure. This article reviews available evidence for the use of pegaspargase in pediatric acute lymphoblastic leukemia.

Keywords: asparagine, asparaginase, serum asparaginase activity, toxicity

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