Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review

Cynthia Bender,1 Luke Maese,2 Maria Carter-Febres,2 Anupam Verma2 1Department of Pharmacy, Primary Children’s Hospital, Salt Lake City, UT, USA; 2Division of Hematology/Oncology, Department of Pediatrics, University of Utah and Primary Children’s Hospital, Salt Lake City, UT, USA...

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Autores principales:	Bender C, Maese L, Carter-Febres M, Verma A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	asparagine asparaginase serum asparaginase activity toxicity Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/81fb1708304549eeb522f730dfa55832
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spelling	oai:doaj.org-article:81fb1708304549eeb522f730dfa558322021-12-02T15:54:01ZClinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review1179-9889https://doaj.org/article/81fb1708304549eeb522f730dfa558322021-04-01T00:00:00Zhttps://www.dovepress.com/clinical-utility-of-pegaspargase-in-children-adolescents-and-young-adu-peer-reviewed-fulltext-article-BLCTThttps://doaj.org/toc/1179-9889Cynthia Bender,1 Luke Maese,2 Maria Carter-Febres,2 Anupam Verma2 1Department of Pharmacy, Primary Children’s Hospital, Salt Lake City, UT, USA; 2Division of Hematology/Oncology, Department of Pediatrics, University of Utah and Primary Children’s Hospital, Salt Lake City, UT, USACorrespondence: Anupam VermaPediatric Hematology/Oncology, University of Utah, Primary Children’s Hospital, 100 N Mario Capecchi Drive, Salt Lake City, UT, 84113, USATel +1 801 662 4700Fax +1 801 662 4707Email anupam.verma@hsc.utah.eduAbstract: Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi, have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts. Pegaspargase, a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase, has become an integral component of pediatric upfront and relapsed ALL protocols due to its longer half-life and improved immunogenicity profile compared to native asparaginase preparations. Over the past two decades great strides have been made in outcomes for pediatric ALL due to risk stratification, incorporation of multiagent chemotherapy protocols, and central nervous system prophylaxis with pegaspargase having played an important role in this success. However, adolescents and young adults (AYA) with ALL when treated on contemporaneous trials using adult ALL regimens, continue to have poor outcomes. There is increasing realization of adapting pediatric trial regimens for treating AYAs, especially those incorporating higher intensity of chemotherapeutic agents with pegaspargase being one such agent. Dose or treatment-limiting toxicity is observed in 25– 30% of patients, most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis, and dyslipidemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival leading to higher risk of relapse, and in cases of relapse, a higher risk for remission failure. This article provides an overview of available evidence for use of pegaspargase in pediatric acute lymphoblastic leukemia.Keywords: asparagine, asparaginase, serum asparaginase activity, toxicityBender CMaese LCarter-Febres MVerma ADove Medical Pressarticleasparagineasparaginaseserum asparaginase activitytoxicityDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol Volume 11, Pp 25-40 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	asparagine asparaginase serum asparaginase activity toxicity Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	asparagine asparaginase serum asparaginase activity toxicity Diseases of the blood and blood-forming organs RC633-647.5 Bender C Maese L Carter-Febres M Verma A Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
description	Cynthia Bender,1 Luke Maese,2 Maria Carter-Febres,2 Anupam Verma2 1Department of Pharmacy, Primary Children’s Hospital, Salt Lake City, UT, USA; 2Division of Hematology/Oncology, Department of Pediatrics, University of Utah and Primary Children’s Hospital, Salt Lake City, UT, USACorrespondence: Anupam VermaPediatric Hematology/Oncology, University of Utah, Primary Children’s Hospital, 100 N Mario Capecchi Drive, Salt Lake City, UT, 84113, USATel +1 801 662 4700Fax +1 801 662 4707Email anupam.verma@hsc.utah.eduAbstract: Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi, have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts. Pegaspargase, a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase, has become an integral component of pediatric upfront and relapsed ALL protocols due to its longer half-life and improved immunogenicity profile compared to native asparaginase preparations. Over the past two decades great strides have been made in outcomes for pediatric ALL due to risk stratification, incorporation of multiagent chemotherapy protocols, and central nervous system prophylaxis with pegaspargase having played an important role in this success. However, adolescents and young adults (AYA) with ALL when treated on contemporaneous trials using adult ALL regimens, continue to have poor outcomes. There is increasing realization of adapting pediatric trial regimens for treating AYAs, especially those incorporating higher intensity of chemotherapeutic agents with pegaspargase being one such agent. Dose or treatment-limiting toxicity is observed in 25– 30% of patients, most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis, and dyslipidemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival leading to higher risk of relapse, and in cases of relapse, a higher risk for remission failure. This article provides an overview of available evidence for use of pegaspargase in pediatric acute lymphoblastic leukemia.Keywords: asparagine, asparaginase, serum asparaginase activity, toxicity
format	article
author	Bender C Maese L Carter-Febres M Verma A
author_facet	Bender C Maese L Carter-Febres M Verma A
author_sort	Bender C
title	Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
title_short	Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
title_full	Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
title_fullStr	Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
title_full_unstemmed	Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review
title_sort	clinical utility of pegaspargase in children, adolescents and young adult patients with acute lymphoblastic leukemia: a review
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/81fb1708304549eeb522f730dfa55832
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Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review

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