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Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172)

Lookup NU author(s): Professor Christine Harrison FRCPath FMedSci

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Abstract

Concern about late adverse effects of cranial radiotherapy (XRT) has led to alternative approaches to eliminate leukaemia from the central nervous system (CNS) in childhood acute lymphoblastic leukaemia (ALL). The Medical Research Council UKALL XI trial recruited 2090 children with ALL between 1990 and 1997. Median follow-up is 7 years 9 months; event-free survival (EFS) and overall survival were 63.1% and 84.6%, respectively, at 5 years and 59.8% and 79.4% at 10 years. The isolated CNS relapse rate was 7.0% at 10 years. Patients were randomized for CNS-directed therapy within white blood cell (WBC) groups. For WBC <50 x 10(9)/l, high-dose intravenous methotrexate (HDMTX) (6-8 g/m2) with intrathecal methotrexate (ITMTX) was compared with ITMTX alone, and was significantly better at preventing isolated and combined CNS relapse, but non-CNS relapses were similar. There was no significant difference in EFS at 10 years, 64.1% [95% confidence interval (CI) 60.4-67.8] with HDMTX plus ITMTX, and 63.0% (95% CI 59.5-66.5) with ITMTX alone. For WBC >/=50 x 10(9)/l, HDMTX with ITMTX was compared with XRT and a short course of ITMTX. CNS relapses were significantly fewer with XRT, but there was a non-significant increase in non-CNS relapses. EFS was not significantly different, being 55.2% (95% CI 47.8-62.6) at 10 years with XRT and 52.1% (95% CI 44.8-59.4) with HDMTX plus ITMTX.

Publication metadata

Author(s): Hill FG, Richards S, Gibson B, Hann I, Lilleyman J, Kinsey S, Mitchell C, Harrison CJ, Eden OB

Publication type: Article

Publication status: Published

Journal: British Journal of Haematology

Year: 2004

Volume: 124

Issue: 1

Pages: 33-46

ISSN (print): 0007-1048

ISSN (electronic): 1365-2141

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1046/j.1365-2141.2003.04738.x

DOI: 10.1046/j.1365-2141.2003.04738.x

Notes: The UK Medical Research Council Working Party on Childhood Leukaemia Clinical Trial Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't England

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