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Reinduction Platform for Children With First Marrow Relapse of Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

Elizabeth A. Raetz, Michael J. Borowitz, Meenakshi Devidas, Stephen B. Linda, Stephen P. Hunger, Naomi J. Winick, Bruce M. Camitta, Paul S. Gaynon, William L. Carroll

From the New York University Cancer Institute and Department of Pediatrics, New York University, New York, NY; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD; Children's Oncology Group and University of Florida, Gainesville, FL; Department of Pediatrics, University of Colorado Denver and Health Science Center and The Children's Hospital, Aurora, CO; Department of Pediatrics, University of Texas Southwestern, Dallas, TX; Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee, WI; and the Children's Hospital of Los Angeles, Los Angeles, CA

Corresponding author: Elizabeth A. Raetz, MD, New York University School of Medicine, Hassenfeld Children's Center for Cancer and Blood Disorders, 160 E 32nd St, New York, NY 10016; e-mail: elizabeth.raetz{at}nyumc.org

Purpose Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials.

Patients and Methods One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; < 36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block.

Results Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68% ± 6% for ER (n = 63) and 96% ± 3% for LR (n = 54; P < .0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of block 1 in 75% ± 7% of ER (n = 36) versus 51% ± 8% of LR (n = 43; P = .0375) and 12-month event-free survival was 80% ± 7% versus 58% ± 7% in MRD-negative versus positive patients (P < .0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4%) from infections.

Conclusion The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.

Supported in part by Children's Oncology Group Grants No. U10 CA98543 and R21CA110344 (M.J.B.) from the National Cancer Institute.

Presented in part at the Annual Meeting of the American Society of Hematology, Orlando, FL, December 9-12, 2006.

E.A.R. and M.J.B. contributed equally to this article.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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