The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia: Lessons from the NOPHO ALL-92 and ALL-2000 protocols

Pediatr Blood Cancer. 2017 Feb;64(2):242-249. doi: 10.1002/pbc.26191. Epub 2016 Oct 17.

Abstract

Background: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy.

Procedures: Retrospectively, we estimated the effect of CNS involvement and CNS-RT on events and overall survival (OS) in 835 children treated for high-risk ALL in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000 trials.

Results: We did not observe a statistically significant difference in the OS or event-free survival (EFS) in patients with CNS involvement at diagnosis, but the risk of isolated CNS relapse was higher (hazard ratio [HR] 7.09, P < 0.001). CNS-RT was given to 169 of the 783 patients in first complete remission, of which 16 had CNS involvement at diagnosis. In general, CNS-RT improved EFS (HR 0.58, P < 0.05) but not OS (HR 0.69, P = n.s.). The adjusted HRs for all relapses, isolated bone marrow relapse, CNS-involving relapse, and isolated CNS relapse, were 0.47 (P < 0.01), 0.50 (P < 0.05), 0.34 (P < 0.01), and 0.12 (P < 0.01), respectively, in irradiated patients.

Conclusions: CNS-RT was associated with an advantage in EFS by decreasing the risk of relapse but without improving OS.

Keywords: acute lymphoblastic leukemia; central nervous system; children; irradiation; risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Central Nervous System Neoplasms / etiology
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / radiotherapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / radiotherapy*
  • Neoplasm Staging
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Rate