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The outcomes of Central Nervous System (CNS) relapses in children with acute lymphoblastic leukaemia (ALL) treated in the ALL R3 trial, between January 2003 and March 2011 were analysed. Patients were risk stratified, to receive a matched donor allogeneic transplant or fractionated cranial irradiation with continued treatment for two years. A randomisation of Idarubicin with Mitoxantrone closed in December 2007 in favour of Mitoxantrone. The estimated 3-year progression free survival for combined and isolated CNS disease were 40.6% (25·1, 55·6) and 38.0% (26.2, 49.7) respectively. Univariate analysis showed a significantly better survival for age <10 years, progenitor-B cell disease, good-risk cytogenetics and those receiving Mitoxantrone. Adjusting for these variables (age, time to relapse, cytogenetics, treatment drug and gender) a multivariate analysis, showed a poorer outcome for those with combined CNS relapse (HR 2·64, 95% CI 1·32, 5·31, p = 0·006 for OS). ALL R3 showed an improvement in outcome for CNS relapses treated with Mitoxantrone compared to Idarubicin; a potential benefit for matched donor transplant for those with very early and early isolated-CNS relapses.Controlled-Trials.com ISRCTN45724312.

Original publication

DOI

10.1371/journal.pone.0108107

Type

Journal article

Journal

PloS one

Publication Date

01/2014

Volume

9

Addresses

Children's Cancer Group, Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer, Manchester Academic Health Science Centre, Central Manchester University Hospitals Foundation Trust, The University of Manchester, Manchester, United Kingdom.

Keywords

Bone Marrow, Humans, Central Nervous System Neoplasms, Neoplasm Recurrence, Local, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Transplantation, Homologous, Odds Ratio, Risk Factors, Cohort Studies, Adolescent, Child, Child, Preschool, Female, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Chemoradiotherapy