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

TY - JOUR

T1 - The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia

T2 - Lessons from the NOPHO ALL-92 and ALL-2000 protocols

AU - Taskinen, Mervi

AU - Oskarsson, Trausti

AU - Levinsen, Mette

AU - Bottai, Matteo

AU - Hellebostad, Marit

AU - Jonsson, Olafur Gisli

AU - Lähteenmäki, Päivi

AU - Schmiegelow, Kjeld

AU - Heyman, Mats

N1 - © 2016 Wiley Periodicals, Inc.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Central Nervous System Neoplasms/etiology

KW - Child

KW - Child, Preschool

KW - Combined Modality Therapy

KW - Cranial Irradiation

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Infant

KW - Male

KW - Neoplasm Recurrence, Local/etiology

KW - Neoplasm Staging

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications

KW - Prognosis

KW - Retrospective Studies

KW - Survival Rate

U2 - 10.1002/pbc.26191

DO - 10.1002/pbc.26191

M3 - Journal article

C2 - 27748030

SN - 1545-5009

VL - 64

SP - 242

EP - 249

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

IS - 2

ER -