title: Outcome of central nervous system relapses in childhood acute lymphoblastic leukaemia--prospective open cohort analyses of the ALLR3 trial.
abstract: 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.
  
  
  BACKGROUND
  Controlled-Trials.com ISRCTN45724312.
authors.affiliation: 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.
authors.forename: Ashish Narayan
authors.initials: AN
authors.lastname: Masurekar
authors.affiliation: 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.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: Parker
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Milensu
authors.initials: M
authors.lastname: Shanyinde
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.affiliation: Bristol Genetics Laboratory, Southmead Hospital, Bristol, United Kingdom.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Hancock
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ancliff
authors.affiliation: Child Oncology and Haematology Centre, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Goulden
authors.affiliation: Queensland Children's Cancer Centre, Brisbane, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Childrens Hospital, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Dutch Childhood Oncology Group, The Hague, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hoogerbrugge
authors.affiliation: Department of Haematology-Oncology, SA Pathology at Women's and Children's Hospital and University of Adelaide, Adelaide, Australia.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Department of Haematology, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Darbyshire
authors.affiliation: Paediatric Oncology, Tata Translational Cancer Research Centre, Kolkata, India.
authors.forename: Shekhar
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Love
authors.affiliation: Paediatric Oncology, Tata Translational Cancer Research Centre, Kolkata, India.
authors.forename: Vaskar
authors.initials: V
authors.lastname: Saha
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome