title: 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.
authors.affiliation: Leukemia Section, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. meir.wetzler@roswellpark.org
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Ben L
authors.initials: BL
authors.lastname: Sanford
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Divino
authors.initials: D
authors.lastname: DeOliveira
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001215:Asparaginase / Q000627:therapeutic use*; D001216:Asparagine / Q000097:blood*; D005240:Feasibility Studies; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001216:Asparagine; C042705:pegaspargase; D001215:Asparaginase