CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951

• Published in: Archives de pédiatrie : organe officiel de la Société française de pédiatrie Vol. 28; no. 5; pp. 411 - 416
• Main Authors: Sirvent, N., Suciu, S., De Moerloose, B., Ferster, A., Mazingue, F., Plat, G., Yakouben, K., Uyttebroeck, A., Paillard, C., Costa, V., Simon, P., Pluchart, C., Poirée, M., Minckes, O., Millot, F., Freycon, C., Maes, P., Hoyoux, C., Cavé, H., Rohrlich, P., Bertrand, Y., Benoit, Y.
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.07.2021; Elsevier
• Subjects: Acute lymphoblastic leukemia; Adolescent; Biomarkers, Tumor; Cancer; Central Nervous System; Child; Child, Preschool; Children; Cranial Irradiation; Female; Hematology; Human health and pathology; Humans; Infant; Life Sciences; Male; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prognosis; Treatment Outcome; Acute lymphoblastic leukemia; Central nervous system; Children
• ISSN: 0929-693X; 1769-664X
• DOI: 10.1016/j.arcped.2021.04.009

To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial. From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients. The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse. CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728.