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Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511.

Abstract
CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.
AuthorsMeir Wetzler, Ben L Sanford, Joanne Kurtzberg, Divino DeOliveira, Stanley R Frankel, Bayard L Powell, Jonathan E Kolitz, Clara D Bloomfield, Richard A Larson
JournalBlood (Blood) Vol. 109 Issue 10 Pg. 4164-7 (May 15 2007) ISSN: 0006-4971 [Print] United States
PMID17264295 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Polyethylene Glycols
  • Asparagine
  • pegaspargase
  • Asparaginase
Topics
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents (therapeutic use)
  • Asparaginase (therapeutic use)
  • Asparagine (blood)
  • Feasibility Studies
  • Humans
  • Immunophenotyping
  • Middle Aged
  • Polyethylene Glycols (therapeutic use)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (blood, drug therapy, mortality)
  • Survival Analysis
  • Treatment Outcome

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