Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F22%3A10418895" target="_blank" >RIV/00064203:_____/22:10418895 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qn7kWuHlfk" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qn7kWuHlfk</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3324/haematol.2020.258525" target="_blank" >10.3324/haematol.2020.258525</a>
Alternative languages
Result language
angličtina
Original language name
Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia
Original language description
Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples of 701 children, 673 with primary ALL, 28 with relapsed ALL, and 188 adults with primary ALL were analyzed for anti-PEG IgG and IgM. Measurements in 58 healthy infants served as reference to define cut-points for antibody-positive and -negative samples. Anti-PEG antibodies were detected in ALL patients prior the first PEG-ASNase with a prevalence of 13.9% (anti-PEG IgG) and 29.1% (anti-PEG IgM). After administration of PEG-ASNase the prevalence of anti-PEG antibodies decreased to 4.2% for anti-PEG IgG and to 4.5% for anti-PEG IgM. Pre-existing anti-PEG antibodies did not inhibit PEG-ASNase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner. Although pre-existing anti-PEG antibodies did not boost, pre-existing anti-PEG IgG were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2) (p<0.01; Fisher's exact test). Two of 4 patients with pre-existing anti-PEG IgG and first-exposure hypersensitivity reactions were not switched to Erwinia ASNase and continued on PEG-ASNase with sufficient activities (>=100U/L). Pre-existing anti-PEG antibodies were detected in a considerable proportion of patients with ALL, did not inhibit PEG-ASNase activity but were associated with lower serum PEGASNase activity levels. Patients with pre-existing antibodies may show mild to moderate signs of hypersensitivity reaction after their first PEG-ASNase, which may be successfully addressed by re-challenge.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Haematologica
ISSN
0390-6078
e-ISSN
1592-8721
Volume of the periodical
107
Issue of the periodical within the volume
1
Country of publishing house
IT - ITALY
Number of pages
9
Pages from-to
49-57
UT code for WoS article
000740550800009
EID of the result in the Scopus database
2-s2.0-85097916055