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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4164-4167.
Prepublished online as a Blood First Edition Paper on January 30, 2007; DOI 10.1182/blood-2006-09-045351.


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CLINICAL TRIALS AND OBSERVATIONS

Brief Report

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

Meir Wetzler1, Ben L. Sanford2, Joanne Kurtzberg3, Divino DeOliveira3, Stanley R. Frankel4, Bayard L. Powell5, Jonathan E. Kolitz6, Clara D. Bloomfield7, and Richard A. Larson8

1 Leukemia Section, Roswell Park Cancer Institute, Buffalo, NY; 2 Cancer and Leukemia Group B (CALGB) Biostatistics, Duke University Medical Center, Durham, NC; 3 Duke University Medical Center, Durham, NC; 4 Marlene and Stewart Greenebaum Cancer Center, University of Maryland Cancer Center, Baltimore; 5 Wake Forest University School of Medicine, Winston-Salem, NC; 6 North Shore University Hospital, Manhasset, NY; 7 Ohio State University Comprehensive Cancer Center, Columbus; 8 University of Chicago, IL

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.


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