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

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Mervi Taskinen, Trausti Oskarsson, Mette Levinsen, Matteo Bottai, Marit Hellebostad, Olafur Gisli Jonsson, Päivi Lähteenmäki, Kjeld Schmiegelow, Mats Heyman

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.

Original languageEnglish
JournalPediatric Blood & Cancer
Issue number2
Pages (from-to)242-249
Number of pages8
Publication statusPublished - Feb 2017

    Research areas

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

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