Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patients
BACKGROUND. Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti‐PEG) was previously re...
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| Published in | Cancer Vol. 110; no. 1; pp. 103 - 111 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.07.2007
Wiley-Liss |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0008-543X 1097-0142 |
| DOI | 10.1002/cncr.22739 |
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| Abstract | BACKGROUND.
Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti‐PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti‐PEG was associated with rapid clearance PEG‐ASNase.
METHODS.
The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin‐Frankfurt‐Muenster 2000 studies. Twenty‐eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG‐ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti‐PEG using 2 techniques: 1) serology, by agglutination of PEG‐coated red blood cells; 2) flow cytometry, by analysis of 10 μm PEG beads stained for bound immunoglobulins.
RESULTS.
Of the 15 sera from PEG‐ASNase‐treated patients with undetectable ASNase activity, anti‐PEG was detected in 9 by serology and in 12 by flow cytometry. Anti‐PEG was detected in 1 PEG‐ASNase‐treated patient with lower ASNase activity (123 U/L). No relation was observed between anti‐PEG and serum ASNase activity for patients treated with unmodified ASNase.
CONCLUSIONS.
The presence of anti‐PEG was very closely associated with rapid clearance of PEG‐ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti‐PEG on PEG‐conjugated agents. Screening and monitoring for anti‐PEG may allow identification of patients for whom a modified dosing strategy or use of a non‐PEGylated drug would be appropriate. Cancer 2007. © 2007 American Cancer Society.
Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia. The presence of antibody specific to poly(ethylene glycol) was very closely associated with undetectable serum ASNase activity in PEG‐ASNase‐treated patients. |
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| AbstractList | Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti-PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti-PEG was associated with rapid clearance PEG-ASNase.BACKGROUNDRapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti-PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti-PEG was associated with rapid clearance PEG-ASNase.The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin-Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by agglutination of PEG-coated red blood cells; 2) flow cytometry, by analysis of 10 microm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1 PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was observed between anti-PEG and serum ASNase activity for patients treated with unmodified ASNase.METHODSThe investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin-Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by agglutination of PEG-coated red blood cells; 2) flow cytometry, by analysis of 10 microm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1 PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was observed between anti-PEG and serum ASNase activity for patients treated with unmodified ASNase.The presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate.CONCLUSIONSThe presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate. Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti-PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti-PEG was associated with rapid clearance PEG-ASNase. The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin-Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by agglutination of PEG-coated red blood cells; 2) flow cytometry, by analysis of 10 microm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1 PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was observed between anti-PEG and serum ASNase activity for patients treated with unmodified ASNase. The presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate. BACKGROUND. Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti‐PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti‐PEG was associated with rapid clearance PEG‐ASNase. METHODS. The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin‐Frankfurt‐Muenster 2000 studies. Twenty‐eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG‐ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti‐PEG using 2 techniques: 1) serology, by agglutination of PEG‐coated red blood cells; 2) flow cytometry, by analysis of 10 μm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG‐ASNase‐treated patients with undetectable ASNase activity, anti‐PEG was detected in 9 by serology and in 12 by flow cytometry. Anti‐PEG was detected in 1 PEG‐ASNase‐treated patient with lower ASNase activity (123 U/L). No relation was observed between anti‐PEG and serum ASNase activity for patients treated with unmodified ASNase. CONCLUSIONS. The presence of anti‐PEG was very closely associated with rapid clearance of PEG‐ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti‐PEG on PEG‐conjugated agents. Screening and monitoring for anti‐PEG may allow identification of patients for whom a modified dosing strategy or use of a non‐PEGylated drug would be appropriate. Cancer 2007. © 2007 American Cancer Society. Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia. The presence of antibody specific to poly(ethylene glycol) was very closely associated with undetectable serum ASNase activity in PEG‐ASNase‐treated patients. |
| Author | Chan, Linda S. Armstrong, Jonathan K. Fisher, Timothy Meiselman, Herbert J. Koling, Susanne Hempel, Georg Garratty, George |
| Author_xml | – sequence: 1 givenname: Jonathan K. surname: Armstrong fullname: Armstrong, Jonathan K. email: jonathan.armstrong@usc.edu – sequence: 2 givenname: Georg surname: Hempel fullname: Hempel, Georg – sequence: 3 givenname: Susanne surname: Koling fullname: Koling, Susanne – sequence: 4 givenname: Linda S. surname: Chan fullname: Chan, Linda S. – sequence: 5 givenname: Timothy surname: Fisher fullname: Fisher, Timothy – sequence: 6 givenname: Herbert J. surname: Meiselman fullname: Meiselman, Herbert J. – sequence: 7 givenname: George surname: Garratty fullname: Garratty, George |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18848918$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/17516438$$D View this record in MEDLINE/PubMed |
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| CODEN | CANCAR |
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Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute... Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia... |
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| SubjectTerms | acute lymphoblastic leukemia Agglutination Tests - methods Antibodies - blood antibody Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - therapeutic use Asparaginase - immunology Asparaginase - pharmacokinetics Asparaginase - therapeutic use asparaginase medac Biological and medical sciences Child Female Flow Cytometry - methods Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Metabolic Clearance Rate Oncaspar PEG‐asparaginase poly(ethylene glycol) Polyethylene Glycols - pharmacokinetics Polyethylene Glycols - therapeutic use Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Reproducibility of Results Treatment Outcome Tumors |
| Title | Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patients |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcncr.22739 https://www.ncbi.nlm.nih.gov/pubmed/17516438 https://www.proquest.com/docview/70666764 |
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