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Isolated CNS Relapse of Acute Lymphoblastic Leukemia Treated With Intensive Systemic Chemotherapy and Delayed CNS Radiation: A Pediatric Oncology Group Study

Julio C. Barredo, Meenakshi Devidas, Stephen J. Lauer, Amy Billett, MaryAnne Marymont, Jeanette Pullen, Bruce Camitta, Naomi Winick, William Carroll, A. Kim Ritchey

From the Department of Pediatrics, Medical University of South Carolina, Charleston, SC; Children's Oncology Group Statistics & Data Center, University of Florida, Gainesville, FL; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Department of Pediatrics, Dana-Farber Cancer Institute, Boston, MA; Radiation/Oncology, Northwestern University, Chicago, IL; Department of Pediatrics, University of Mississippi, Jackson, MS; Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee, WI; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX; Department of Pediatrics, New York University Medical Center, New York, NY; and the Division of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA

Address reprint requests to Julio C. Barredo, MD, Pediatric Hematology-Oncology, MUSC Children's Hospital, 135 Rutledge Ave, Charleston, SC 29425; e-mail: barredjc{at}musc.edu

PURPOSE: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration.

PATIENTS AND METHODS: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window.

RESULTS: Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% ± 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% ± 11.3% and 77.7% ± 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% ± 10.8% and 80.2% ± 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported.

CONCLUSION: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential con- flicts of interest and author contributions are found at the end of this article.

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