Mervi Taskinen1, Trausti Oskarsson2,3, Mette Levinsen4,5, Matteo Bottai6, Marit Hellebostad7, Olafur Gisli Jonsson8, Päivi Lähteenmäki9, Kjeld Schmiegelow4,5, Mats Heyman2,3. 1. Division of Pediatric Hematology-Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland. 2. Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden. 3. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. 4. Institute of Gynegology, Obstetrics, and Pediatrics, University of Copenhagen, Copenhagen, Denmark. 5. Department of Pediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark. 6. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 7. Department of Pediatrics, Drammen Hospital, Oslo, Norway. 8. Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 9. Children's Hospital, Turku University Hospital, Turku, Finland.
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.
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.