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Author Notes:

Correspondence Donna Johnston, Division of Hematology/Oncology, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, K1H8L1 Canada. djohnston@cheo.on.ca

The authors declare that there is no conflict of interest.

Subjects:

Research Funding:

The research reported in this publication was supported by the Children’s Oncology Group, National Cancer Institute of the National Institutes of Health under award numbers U10CA180886, U10CA180899, U10CA098543, U10CA098413, and St. Baldrick’s Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Pediatrics
  • AML
  • CNS
  • therapy
  • BONE-MARROW-TRANSPLANTATION
  • CANCER GROUP
  • RISK-FACTORS
  • INVOLVEMENT
  • DIAGNOSIS
  • ADOLESCENTS
  • MANAGEMENT
  • SURVIVAL
  • OUTCOMES
  • RELAPSE

Central nervous system disease in pediatric acute myeloid leukemia: A report from the Children's Oncology Group

Journal Title:

Pediatric Blood and Cancer

Volume:

Volume 64, Number 12

Publisher:

, Pages e26612-e26612

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: The prognostic impact of central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) has varied in past trials, and controversy exists over the degree of involvement requiring intensified CNS therapy. Two recent Children's Oncology Group protocols, AAML03P1 and AAML0531, directed additional intrathecal (IT) therapy to patients with CNS2 (≤5 white blood cell [WBC] with blasts) or CNS3 ( > 5 WBC with blasts or CNS symptoms) disease at diagnosis. Methods: We examined disease characteristics and outcomes of the 1,344 patients on these protocols, 949 with CNS1 (no blasts), 217 with CNS2, and 178 with CNS3, with the latter two receiving additional IT therapy. Results: Young age (P = 0.003), hyperleukocytosis (P  < 0.001), and the presence of inversion 16 (P  < 0.001) were the only factors more prevalent in patients with CNS2 or CNS3 disease. Complete remission at the end of induction (EOI) 2 was achieved less often in patients with CNS involvement (P  < 0.001). From diagnosis, event-free survival (EFS) for patients with CNS involvement was significantly worse (P  < 0.001), whereas overall survival (OS) was not (P = 0.16). From the EOI1, there was a higher relapse rate (RR) and worse disease-free survival (DFS), but less impact on OS (CNS1:DFS 58.9%, RR 34.1%, OS 69.3%; CNS2:DFS 53.2%, RR 40.9%, OS 74.7%; CNS3:DFS 45.2%, RR 48.8%, OS 60.8%; P = 0.006, P  < 0.001, P = 0.045, respectively). Multivariable analysis showed that independently CNS2 and CNS3 status adversely affected RR and DFS. Traumatic diagnostic lumbar puncture was not associated with worse outcome. Conclusions: CNS leukemia confers greater relapse risk despite more aggressive locally directed therapy. Novel approaches need to be investigated in this group of patients.

Copyright information:

© 2017 Wiley Periodicals, Inc.

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