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Article: Asparagine synthetase polymorphisms and toxicity and efficacy of asparaginases.

Avramis, Vassilios I

Clinical cancer research : an official journal of the American Association for Cancer Research

2015 Volume 21, Issue 2, Page(s) 230–232

Abstract: Asparaginases develop innovative "tumor starvation" conditions for all antileukemia treatments; however, administrations are limited by the toxicities of this drug. Patients exhibiting moderate toxicity have optimal treatment outcomes. Certain asparagine ...

Abstract	Asparaginases develop innovative "tumor starvation" conditions for all antileukemia treatments; however, administrations are limited by the toxicities of this drug. Patients exhibiting moderate toxicity have optimal treatment outcomes. Certain asparagine synthetase polymorphisms may contribute to severe host toxicities in divergent subsets of patients, whereas others do not. Clinical correlations should be evaluated.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Asparaginase/adverse effects ; Aspartate-Ammonia Ligase/genetics ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Chemical Substances	Antineoplastic Agents ; Asparaginase (EC 3.5.1.1) ; Aspartate-Ammonia Ligase (EC 6.3.1.1)
Language	English
Publishing date	2015-01-15
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-14-1714
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Article ; Online: Is glutamine depletion needed in ALL disease?

Avramis, Vassilios I

Blood

2014 Volume 123, Issue 23, Page(s) 3532–3533

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Asparaginase/therapeutic use ; Aspartate-Ammonia Ligase/genetics ; Glutaminase/chemistry ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Chemical Substances	Antineoplastic Agents ; Asparaginase (EC 3.5.1.1) ; Glutaminase (EC 3.5.1.2) ; Aspartate-Ammonia Ligase (EC 6.3.1.1)
Language	English
Publishing date	2014-06-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2014-04-565523
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Article ; Online: Asparaginases: biochemical pharmacology and modes of drug resistance.

Avramis, Vassilios I

Anticancer research

2012 Volume 32, Issue 7, Page(s) 2423–2437

Abstract: This is an ambitious effort attempting to present as many aspects as possible in a review article on asparaginases (ASNase), and their use against acute lymphoblastic leukemia (ALL) and T-cell lymphomas. In the process, the modes of drug resistance are ... ...

Abstract	This is an ambitious effort attempting to present as many aspects as possible in a review article on asparaginases (ASNase), and their use against acute lymphoblastic leukemia (ALL) and T-cell lymphomas. In the process, the modes of drug resistance are described both of the host and in the leukemia cells themselves. These modes of drug resistance, developed by the ALL cells, are an attempt to overcome the toxic insult this class of anti-leukemic drugs causes to them. It is expected that by reading this article one would obtain a better understanding of the initial events in the leukemia development, its microenvironment, and the many issues that a leukemia specialist has to deal with, especially in the treatment of refractory and relapsed patient populations. The specific issues addressed in this review deal with the importance of nutrients in tumor growth and progression of malignancies; the cytogenetics of ALL, as well as its chemotherapy, are also briefly presented. The emphasis will turn to ASNase, their mechanisms of action, the immune responses they cause in a significant percentage of the ALL patients, the significance of the up-regulation of glutamine synthetase and asparagine synthetase and the complexity of the elucidation of the mechanisms of action of ASNase. Additional details on the ASNase epitope mapping of anti-ASNase antibodies, the degradation of the protein, and the unmet needs in producing an optimal ASNase protein, will be also presented. Finally, a brief description of the toxicity, as well as the correlative factor of ALL treatment with ASNase is given.
MeSH term(s)	Adolescent ; Asparaginase/pharmacology ; Child ; Drug Resistance, Neoplasm ; Humans ; Lymphoma, T-Cell/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Young Adult
Chemical Substances	Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2012-07
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: Asparaginases: a successful class of drugs against leukemias and lymphomas.

Avramis, Vassilios I

Journal of pediatric hematology/oncology

2011 Volume 33, Issue 8, Page(s) 573–579

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Asparaginase/therapeutic use ; Drug Design ; Energy Metabolism/drug effects ; Energy Metabolism/physiology ; Escherichia coli Proteins/therapeutic use ; Glutamine/metabolism ; Humans ; Leukemia/drug therapy ; Leukemia/metabolism ; Lymphoma/drug therapy ; Lymphoma/metabolism
Chemical Substances	Antineoplastic Agents ; Escherichia coli Proteins ; Glutamine (0RH81L854J) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2011-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/MPH.0b013e31823313be
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Zs.A 1537: Show issues

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Article: Clinical pharmacology of asparaginases in the United States: asparaginase population pharmacokinetic and pharmacodynamic (PK-PD) models (NONMEM) in adult and pediatric ALL patients.

Avramis, Vassilios I / Spence, Susan A

Journal of pediatric hematology/oncology

2007 Volume 29, Issue 4, Page(s) 239–247

Abstract: In the past 25 years, effective new drugs along with better treatment decisions based on disease factors have resulted in significantly improved clinical outcomes in acute lymphoblastic leukemia. Despite these successes in the last 2 decades, 15% to 25% ... ...

Abstract	In the past 25 years, effective new drugs along with better treatment decisions based on disease factors have resulted in significantly improved clinical outcomes in acute lymphoblastic leukemia. Despite these successes in the last 2 decades, 15% to 25% of acute lymphoblastic leukemia patients relapse. Therefore, better dosing therapies are still needed. Insights in the pharmacokinetic and pharmacodynamic (PK-PD) contributions of licensed drugs may guide us into better protocol design and optimal use of existing combination drug regimens. Currently, 3 asparaginase formulations are available in the United States, Escherichia coli native asparaginase (ASNase), Pegaspargase, and Erwinase. On the basis of these clinical studies, PK and PD population modeling (NONMEM) have been used to delve into new insights as to the optimal dose, formulation, and time intervals of ASNases that may be used in future clinical trials. Pegaspargase 2500 IU/m2 Q2week dosing seems to be the "golden standard" as far as being safe and effective. Lower doses of this formulation Qweek may achieve better PK "steady-state" profiles in serum. Native E. coli or Erwinia ASNase at 6000 IU/m2 showed inferior PK parameters (peak, trough, and area under the curve) than Pegaspargase. Assuming linear handling of ASNase modeling, simulations of higher doses of these ASNase formulations on a daily or Q48 hours regimen are showing bioequivalency with Pegaspargase PK-PD parameters. Future clinical trial designs may prove these efforts useful.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Asparaginase/administration & dosage ; Asparaginase/pharmacokinetics ; Clinical Trials as Topic ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Retrospective Studies ; United States
Chemical Substances	Antineoplastic Agents ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2007-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/MPH.0b013e318047b79d
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Article ; Online: Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines.

Parmentier, Jean Hugues / Maggi, Maristella / Tarasco, Erika / Scotti, Claudia / Avramis, Vassilios I / Mittelman, Steven D

Leukemia research

2015 Volume 39, Issue 7, Page(s) 757–762

Abstract: L-Asparaginase (ASNase) is a front-line chemotherapy for acute lymphoblastic leukemia (ALL), which acts by deaminating asparagine and glutamine. To evaluate the importance of glutaminase activity, we exploited a recently developed mutant of Helicobacter ... ...

Abstract	L-Asparaginase (ASNase) is a front-line chemotherapy for acute lymphoblastic leukemia (ALL), which acts by deaminating asparagine and glutamine. To evaluate the importance of glutaminase activity, we exploited a recently developed mutant of Helicobacter pylori ASNase (dm HpA), with amino acid substitutions M121C/T169M. The mutant form has the same asparaginase activity as wild-type but lacks glutaminase activity. Wild-type and dm HpA were compared with the clinically used ASNases from Escherichia coli (l-ASP) and Erwinia chrysanthemi (ERWase). Asparaginase activity was similar for all isoforms, while glutaminase activity followed the rank order: ERWase>l-ASP>wild-type HpA>dm HpA. Cytotoxic efficacy of ASNases was tested on 11 human leukemia cell lines and two patient-derived ALL samples. Two cell lines which we had previously shown to be asparagine-dependent were equally sensitive to the asparaginase isoforms. The other nine lines and the two patient-derived samples were more sensitive to isoforms with higher glutaminase activities. ERWase was overall the most effective ASNase on all cell lines tested whereas dm HpA, having the lowest glutaminase activity, was the least effective. These data demonstrate that asparaginase activity alone may not be sufficient for ASNase cytotoxicity, and that glutaminase activity may be required for full anti-leukemic efficacy.
MeSH term(s)	Asparaginase/metabolism ; Cell Line, Tumor ; Glutaminase/metabolism ; Helicobacter pylori/enzymology ; Humans ; Leukemia/pathology
Chemical Substances	Asparaginase (EC 3.5.1.1) ; Glutaminase (EC 3.5.1.2)
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2015.04.008
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Article: Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia.

Avramis, Vassilios I / Tiwari, Prakash Nidhi

International journal of nanomedicine

2006 Volume 1, Issue 3, Page(s) 241–254

Abstract: The discovery of the tumor-inhibitory properties of asparaginase (ASNase) began in the early 1950s with the observation that guinea pig serum-treated lymphoma-bearing mice underwent rapid and often complete regression. About 4000 cases of acute ... ...

Abstract	The discovery of the tumor-inhibitory properties of asparaginase (ASNase) began in the early 1950s with the observation that guinea pig serum-treated lymphoma-bearing mice underwent rapid and often complete regression. About 4000 cases of acute lymphoblastic leukemia (ALL) are diagnosed very year in the US and many more through out the world. The majority of these cases are in children and young adults, making ALL the most common form of malignancy in these age groups. The treatment protocols of ALL are complex and use 6-12 drugs. Consequently, the improvement in the protocol design has improved significantly the success rate for long-term event-free survival in the past 20-30 years, which is now approximately 75% for patients afflicted with the higher risk ALL features and just above this percentage for patients with standard or good features. Despite this success, approximately 15% of patients die from ALL, making leukemic relapse the most common cause of treatment failure in pediatric oncology. ASNases have been the cornerstone of ALL therapies since the late 1970s. Native or pegylated L-asparaginase (ASNase or PEG-ASNase) are highly specific for the deamination of L-asparagine (Asn) to aspartic acid and ammonia. Depletion of Asn leads to a nutritional deprivation and inhibition of protein biosynthesis, resulting in apoptosis in T-lymphoblastic leukemias, which require Asn from external sources. The reactions of the host exposed to repeated ASNase treatments as well as the up-regulation of the mammalian enzymes to overcome the ASN-depletion toxic condition are of significant importance and may make us relearn the lessons on this important antileukemic drug.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Asparaginase/administration & dosage ; Asparaginase/chemistry ; Asparaginase/pharmacokinetics ; Drug Carriers/chemistry ; Humans ; Polyethylene Glycols/chemistry ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; Polyethylene Glycols (30IQX730WE) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2006
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
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Article: Immunogenicity of native or pegylated E. coli and Erwinia asparaginases assessed by ELISA and surface plasmon resonance (SPR-biacore) assays of IgG antibodies (Ab) in sera from patients with acute lymphoblastic leukemia (ALL).

Avramis, Vassilios I / Avramis, Earl V / Hunter, William / Long, Melissa C

Anticancer research

2009 Volume 29, Issue 1, Page(s) 299–302

Abstract: Background: Therapeutic uses of asparaginases (ASNase) have been shown to elicit immune responses resulting in the development of potentially life-threatening human anti-bacterial antibodies (Ab). A robust screening enzyme-linked immunosorbent assay ( ... ...

Abstract	Background: Therapeutic uses of asparaginases (ASNase) have been shown to elicit immune responses resulting in the development of potentially life-threatening human anti-bacterial antibodies (Ab). A robust screening enzyme-linked immunosorbent assay (ELISA) to detect binding Ab(+) against ASNase has been developed and validated for therapeutic monitoring to support clinical trials. Recently, a protein chip bioassay (Biacore) was developed for the Ab of these proteins. These methods were compared. Materials and methods: A Biacore T-100 analyzer using a protein bioassay and an ELISA assay were used to determine the IgG immmuboglobulin Ab against ASNase in sera from 84 acute lymphoblastic leukemia (ALL) patients plus 6 controls (n=121 samples). These samples were characterized for anti-ASNase Ab neutralizing activity. Human E. coli ASNase, pegaspargase and Erwinase proteins were covalently coupled to the carboxy-methylated dextran matrix of a CM5 sensor chip (surface plasmon resonance, SPR). In the course of a nested experimental design, a wide range of human sera from patients who had obvious clinical allergic reactions after either native or pegaspargase treatments were tested. The data were fitted by a parametric logistic equation (+/-95% confidence interval, CI), which ranged from <3.0% to <14%. Results: The specificity of Ab(+) was evaluated using "spiked" human IgG antibodies. Both assays provide near excellent linearity and sensitivity of response (<0.8 to <500 ratio and 1-3000 resonance units [RU]) of anti-ASNase Ab in human sera with low variance. The bioassay method was ten times more sensitive than the ELISA Ab assay. The lowest limit of quantification of Ab(+) ratio for the SPR assay was 0.6 whereas the upper limit of quantification was 3000 RU. The SPR assay results were in excellent accord with both the Ab(-) and the Ab(+). Ab(-) by the ELISA method (<1.003 ratio) was related to a mean RU value of 8.1. Despite the narrow range of ambiguity around the 1.1 Ab(+) ratio values, the majority of the specimens (93.2%) were determined to be Ab(+) by either ELISA or SPR determination. Conclusion: The vast majority (81/84 = 96.4%) of the IgG Ab(+) were neutralizing. The SPR Ab determination technique is reliable, accurate and more sensitive than the ELISA method.
MeSH term(s)	Adult ; Asparaginase/adverse effects ; Asparaginase/immunology ; Asparaginase/therapeutic use ; Child ; Enzyme-Linked Immunosorbent Assay/methods ; Erwinia/enzymology ; Escherichia coli/enzymology ; Humans ; Immunoglobulin G/blood ; Polyethylene Glycols/adverse effects ; Polyethylene Glycols/therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Protein Array Analysis/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Surface Plasmon Resonance/methods
Chemical Substances	Immunoglobulin G ; Polyethylene Glycols (30IQX730WE) ; pegaspargase (7D96IR0PPM) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2009-01
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article: Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: the past, the present and recommendations for the future.

Avramis, Vassilios I / Panosyan, Eduard H

Clinical pharmacokinetics

2005 Volume 44, Issue 4, Page(s) 367–393

Abstract: The discovery of the tumour-inhibitory properties of asparaginase began 50 years ago with the observation that guinea-pig serum-treated lymphoma-bearing mice underwent rapid and often complete regression. Soon afterwards, the asparaginase of bacterial ... ...

Abstract	The discovery of the tumour-inhibitory properties of asparaginase began 50 years ago with the observation that guinea-pig serum-treated lymphoma-bearing mice underwent rapid and often complete regression. Soon afterwards, the asparaginase of bacterial origin was isolated. The asparaginases of bacterial origin induce anti-asparaginase neutralising antibodies in a large proportion of patients (44-60%), thus negating the specific enzymatic activity and resulting in failure of the target amino acid deamination in serum. There is immunological cross-reaction between the antibodies against various formulations of native Escherichia coli-asparaginase and polyethylene glycol (PEG)-asparaginases, but not to Erwinia asparaginase, as suggested by laboratory preclinical findings. This evidence was strongly inferred from the interim analyses in the Children's Cancer Group (CCG)-1961 study. Thus, anti-E. coli or PEG-asparaginase antibodies seropositive patients may benefit from the Erwinia asparaginase. The inter-relationships between asparaginase activity, asparagine (ASN) and glutamine deamination remain largely unexplored in patients. Studies have shown that ASN depletion is insufficient to induce apoptosis in T lymphoblasts in vitro and that the inhibitory concentration of CEM T-cell line is correlated with the asparaginase concentration responsible for 50% glutamine deamination. The optimal catalysis of ASN and glutamine deamination in serum by asparaginase induces apoptosis of leukaemic lymphoblasts. The percentage of ASN and glutamine deamination was predicted by asparaginase activity. Asparaginase activity of 0.1 IU/mL provided insufficient depletion of both amino acids in high-risk acute lymphoblastic leukaemia (ALL) patients. With increasing glutamine deamination, mean asparaginase activities and percentages of post-treatment samples with effective ASN depletion (<3 micromol/L) increase. Both glutamine and ASN deamination are predicted by asparaginase activity. Further population analyses resulted in identification of sigmoid relationships between asparaginase levels and post-treatment glutamine and ASN deamination.Furthermore, pharmacodynamic analyses strongly suggested that >/=90% deamination of glutamine must occur before optimal ASN deamination takes place, due to the de novo ASN biosynthesis by the liver. These pharmacodynamic results from the best-fit population pharmacokinetic/pharmacodynamic model obtained from nonlinear mixed effects model pharmacodynamic analyses for standard-risk ALL patients are similar. These analyses produced the following results: (i) asparaginase activity </=0.4 IU/mL provided insufficient deamination of ASN, whereas >0.4-0.7 IU/mL was required for optimal (90%) ASN and glutamine deamination; and (ii) deamination of glutamine is dependent on asparaginase activity and it correlates with enhanced serum ASN deamination. Thus, glutamine deamination enhances asparaginase efficacy in ALL patients. Deamination of ASN >/=90% of control or ASN concentration <3 micromol/L may be associated with improved survival in this subset of patients. Our findings support the pharmacodynamic mechanism of PEG-asparaginase for disease control in ALL patients. These results taken together strongly support new experimental approaches for application of population pharmacokinetic/pharmacodynamic analyses to further enhance survival of leukaemia patients.
MeSH term(s)	Animals ; Antineoplastic Agents/history ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Asparaginase/administration & dosage ; Asparaginase/history ; Asparaginase/pharmacokinetics ; Asparaginase/pharmacology ; Child ; Clinical Trials as Topic ; Drug Administration Schedule ; Drug Resistance, Neoplasm ; Escherichia coli/enzymology ; History, 20th Century ; History, 21st Century ; Humans ; Pectobacterium chrysanthemi/enzymology ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Chemical Substances	Antineoplastic Agents ; Polyethylene Glycols (30IQX730WE) ; pegaspargase (7D96IR0PPM) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2005
Publishing country	Switzerland
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.2165/00003088-200544040-00003
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Zs.A 1246: Show issues

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Article ; Online: Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children's oncology group report.

Ko, Richard H / Jones, Tamekia L / Radvinsky, David / Robison, Nathan / Gaynon, Paul S / Panosyan, Eduard H / Avramis, Ioannis A / Avramis, Vassilios I / Rubin, Joan / Ettinger, Lawrence J / Seibel, Nita L / Dhall, Girish

Cancer

2015 Volume 121, Issue 23, Page(s) 4205–4211

Abstract: Background: The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ... ...

Abstract	Background: The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. Methods: Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. Results: During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P < .0001) or PEG ASNase (odds ratio, 3.08; P < .0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P = .66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P < .001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P = .68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P = .22) were significantly different. Conclusions: The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.
MeSH term(s)	Antibodies/blood ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/immunology ; Asparaginase/adverse effects ; Asparaginase/chemistry ; Asparaginase/immunology ; Child ; Child, Preschool ; Drug Hypersensitivity/epidemiology ; Drug Hypersensitivity/immunology ; Escherichia coli/enzymology ; Escherichia coli/immunology ; Humans ; Induction Chemotherapy ; Infant ; Pectobacterium chrysanthemi/enzymology ; Pectobacterium chrysanthemi/immunology ; Polyethylene Glycols/chemistry ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Survival Analysis ; Treatment Outcome
Chemical Substances	Antibodies ; Antineoplastic Agents ; Polyethylene Glycols (30IQX730WE) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2015-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.29641
Database	MEDical Literature Analysis and Retrieval System OnLINE

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