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Risk Factors and Therapy for Isolated Central Nervous System Relapse of Pediatric Acute Myeloid Leukemia

From the Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Preventive Medicine, University of Southern California, Los Angeles; Children's Oncology Group, Arcadia, CA; Pediatric Oncology, Children's Hospital of Philadelphia, Philadelphia, PA; and Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University, Atlanta, GA

Address reprint requests to Donna Johnston, MD, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Ontario K1H 8L1, Canada; e-mail: djohnston{at}cheo.on.ca

PURPOSE: CNS relapse of pediatric acute myeloid leukemia (AML) is an infrequent occurrence. This review examines the risk factors and therapy used for patients with an isolated CNS relapse.

PATIENTS AND METHODS: Records of 886 patients with de novo AML were reviewed, and patients who entered remission at the end of one course of therapy and developed an isolated CNS relapse as their first event were analyzed (n = 690).

RESULTS: Thirty-three patients developed an isolated CNS relapse. Factors at diagnosis significantly associated with an isolated CNS relapse, compared with no CNS relapse, included age 0 to 2 years (70% v 27%, respectively; P < .001), enlarged liver (79% v 39%, respectively; P < .001) or spleen (79% v 39%, respectively; P < .001) at diagnosis, CNS disease at diagnosis (33% v 9%, respectively; P < .001), median WBC count (79.2 v 19.3 x 10³ µL, respectively; P < .001), French-American-British M5 morphology (45% v 15%, respectively; P < .001), and chromosome 11 abnormalities (44% v 18%, respectively; P = .022). Treatment of the isolated CNS relapse varied from local therapy with intrathecal chemotherapy and/or radiation therapy to systemic therapy with chemotherapy with or without bone marrow transplantation. Survival rate in the patients treated with local therapy was only 31.5% compared with 21.4% in patients treated with systemic therapy. The 8-year overall survival for patients after an isolated CNS relapse was similar to patients after a bone marrow relapse (26% ± 16% v 21% ± 5%, respectively).

CONCLUSION: Significant predictors for isolated CNS relapse were identified. This study demonstrated that there may be no benefit to systemic therapy versus CNS-directed therapy in outcome. The data support CNS-directed therapy to treat isolated CNS relapse.

Presented at the 18th Annual Meeting of the American Society of Pediatric Hematology/Oncology, Washington, DC, May 13-17, 2005.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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