Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia: Children's Cancer Group Study CCG-1961 Journal Article
| Authors: | Panosyan, E. H.; Seibel, N. L.; Martin-Aragon, S.; Gaynon, P. S.; Avramis, I. A.; Sather, H.; Franklin, J.; Nachman, J.; Ettinger, L. J.; La, M.; Steinherz, P.; Cohen, L. J.; Siegel, S. E.; Avramis, V. I. |
| Article Title: | Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia: Children's Cancer Group Study CCG-1961 |
| Abstract: | We investigated the anti-asparaginase antibody (Ab) and asparaginase enzymatic activity in the sera of 1,001 patients (CCG-1961) with high-risk acute lymphoblastic leukemia (HR-ALL). Patients received nine doses of native Escherichia coli asparaginase during induction. Half of rapid early responders (RER) were randomly assigned to standard intensity arms and continued to receive native asparaginase. The other RER patients and all slow early responders received 6 or 10 doses of PEG-asparaginase. Serum samples (n = 3,193) were assayed for determination of asparaginase Ab titers and enzymatic activity. Three hundred ninety of 1,001 patients (39%) had no elevation of Ab among multiple evaluations-that is, were Ab-negative (<1.1 over negative control)-and 611 patients (61%) had an elevated Ab titer (>1.1). Among these 611 patients, 447 had no measurable asparaginase activity during therapy. Patients who were Ab-positive but had no clinical allergies continued to receive E. coli asparaginase, the activity of which declined precipitately. No detectable asparaginase activity was found in 81 of 88 Ab-positive patients shortly after asparaginase injections (94% neutralizing Ab). The Ab-positive patients with clinical allergies subsequently were given Erwinase and achieved substantial activity (0.1-0.4 IU/ml). An interim analysis of 280 patients who were followed for 30 months from induction demonstrated that the Ab-positive titers during interim maintenance-1 and in delayed intensification-1 were associated with an increased rate of events. The CCG-1961 treatment schedule was very immunogenic, plausibly due to initially administrated native asparaginase. Anti-asparaginase Ab was associated with undetectable asparaginase activity and may be correlated with adverse outcomes in HR ALL. |
| Keywords: | adolescent; child; controlled study; treatment outcome; child, preschool; treatment failure; unclassified drug; major clinical study; prednisone; clinical trial; doxorubicin; drug safety; antineoplastic agents; cytarabine; methotrexate; controlled clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; cyclophosphamide; dexamethasone; vincristine; clinical protocol; dose-response relationship, drug; enzyme activity; enzyme linked immunosorbent assay; acute lymphoblastic leukemia; high risk patient; drug hypersensitivity; standard; infant; immunogenicity; escherichia coli; daunorubicin; asparaginase; immunophenotyping; leukocyte count; antibody detection; antibody; antibody titer; mercaptopurine; arabinoside; neutralizing antibody; cytosine; neutralization tests; pegylated asparaginase; leukemia, lymphocytic, acute; humans; human; male; female; priority journal; article; high-risk acute lymphoblastic leukemia; asparaginase antibody; escherichia coli asparaginase |
| Journal Title: | Journal of Pediatric Hematology/Oncology |
| Volume: | 26 |
| Issue: | 4 |
| ISSN: | 1077-4114 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2004-04-01 |
| Start Page: | 217 |
| End Page: | 226 |
| Language: | English |
| DOI: | 10.1097/00043426-200404000-00002 |
| PROVIDER: | scopus |
| PUBMED: | 15087948 |
| DOI/URL: | |
| Notes: | J. Pediatr. Hematol. Oncol. -- Cited By (since 1996):60 -- Export Date: 16 June 2014 -- CODEN: JPHOF -- Source: Scopus |
