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).
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.
Hill
Frank G H
FG
Department of Clinical & Laboratory Haematology, The Children's Hospital NHS Trust, Birmingham, UK. frank.hill@bch.nhs.uk
Richards
Sue
S
Gibson
Brenda
B
Hann
Ian
I
Lilleyman
John
J
Kinsey
Sally
S
Mitchell
Christopher
C
Harrison
Christine J
CJ
Eden
Osborn B
OB
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008727:Methotrexate / Q000008:administration & dosage*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate