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Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol

Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol
Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol
The single most important prognostic determinant in childhood acute lymphoblastic leukaemia (ALL) is effective therapy and changes in therapy may influence the significance of other risk factors. The effect of intensified therapy on the importance of currently recognized phenotypic and genotypic determinants of outcome was assessed in 2090 children enrolled on the Medical Research Council United Kingdom acute lymphoblastic leukaemia XI (MRC UKALL XI) protocol. Treatment allocation was not determined by risk factors. Multivariate analysis confirmed the dominant influence on prognosis of age, sex and presenting white cell count (WCC). After allowing for these features, blast karyotype, d 8 marrow blast percentage and remission status at the end of induction therapy were the only remaining significant predictors of outcome. Organomegaly, haemoglobin concentration, French–American–British type, body mass index, presence of central nervous system disease at diagnosis, immunophenotype and presence of TEL/AML1 fusion gene (examined in a subset of 659 patients) either had no significant effect on outcome or were significant only in univariate analysis. Among karyotype abnormalities with an independent influence on prognosis, high hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas near haploidy (23–29 chromosomes), presence of the Philadelphia chromosome, t(4;11) and abnormalities affecting the short arm of chromosome 9 [abn (9p)] were adverse risk factors. Early responders to therapy, determined by residual marrow infiltration after 8 d of induction therapy, had a good outcome, while the small proportion of patients who did not achieve a complete remission by the end of induction therapy had a poor outcome. A third block of late intensification was shown to improve event-free survival by 8% at 5 years. The effect of these risk factors was not significantly different between those randomized to the third intensification block and those not randomized to a third block.
0007-1048
103-114
Hann, Ian
acc48ebf-86d1-4ce5-a384-4f628d5d9031
Vora, Ajay
9bf6b2a0-56fc-4797-86ea-d7108280cefc
Harrison, Georgina
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Harrison, Christine
c509c372-2275-44cd-ad07-296a289d6634
Eden, Osborn
94ba1dfb-71f4-4f12-9b6f-32c2d9e7141b
Hill, Frank
795b823b-5560-4190-8e69-169217e456db
Gibson, Brenda
91673809-7015-4a25-b310-2dd5cb7c154a
Richards, Sue
c6716b3c-db48-40e3-a714-219bb8aa91c5
Hann, Ian
acc48ebf-86d1-4ce5-a384-4f628d5d9031
Vora, Ajay
9bf6b2a0-56fc-4797-86ea-d7108280cefc
Harrison, Georgina
7f1eeb94-6734-4d93-8c64-54df46aa49d6
Harrison, Christine
c509c372-2275-44cd-ad07-296a289d6634
Eden, Osborn
94ba1dfb-71f4-4f12-9b6f-32c2d9e7141b
Hill, Frank
795b823b-5560-4190-8e69-169217e456db
Gibson, Brenda
91673809-7015-4a25-b310-2dd5cb7c154a
Richards, Sue
c6716b3c-db48-40e3-a714-219bb8aa91c5

Hann, Ian, Vora, Ajay, Harrison, Georgina, Harrison, Christine, Eden, Osborn, Hill, Frank, Gibson, Brenda and Richards, Sue (2001) Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol. British Journal of Haematology, 113 (1), 103-114. (doi:10.1046/j.1365-2141.2001.02668.x).

Record type: Article

Abstract

The single most important prognostic determinant in childhood acute lymphoblastic leukaemia (ALL) is effective therapy and changes in therapy may influence the significance of other risk factors. The effect of intensified therapy on the importance of currently recognized phenotypic and genotypic determinants of outcome was assessed in 2090 children enrolled on the Medical Research Council United Kingdom acute lymphoblastic leukaemia XI (MRC UKALL XI) protocol. Treatment allocation was not determined by risk factors. Multivariate analysis confirmed the dominant influence on prognosis of age, sex and presenting white cell count (WCC). After allowing for these features, blast karyotype, d 8 marrow blast percentage and remission status at the end of induction therapy were the only remaining significant predictors of outcome. Organomegaly, haemoglobin concentration, French–American–British type, body mass index, presence of central nervous system disease at diagnosis, immunophenotype and presence of TEL/AML1 fusion gene (examined in a subset of 659 patients) either had no significant effect on outcome or were significant only in univariate analysis. Among karyotype abnormalities with an independent influence on prognosis, high hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas near haploidy (23–29 chromosomes), presence of the Philadelphia chromosome, t(4;11) and abnormalities affecting the short arm of chromosome 9 [abn (9p)] were adverse risk factors. Early responders to therapy, determined by residual marrow infiltration after 8 d of induction therapy, had a good outcome, while the small proportion of patients who did not achieve a complete remission by the end of induction therapy had a poor outcome. A third block of late intensification was shown to improve event-free survival by 8% at 5 years. The effect of these risk factors was not significantly different between those randomized to the third intensification block and those not randomized to a third block.

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Published date: 2001

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Local EPrints ID: 26355
URI: http://eprints.soton.ac.uk/id/eprint/26355
ISSN: 0007-1048
PURE UUID: a2065244-44c5-4b13-b04e-0f7d08e13581

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Date deposited: 24 Apr 2006
Last modified: 15 Mar 2024 07:10

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Contributors

Author: Ian Hann
Author: Ajay Vora
Author: Georgina Harrison
Author: Christine Harrison
Author: Osborn Eden
Author: Frank Hill
Author: Brenda Gibson
Author: Sue Richards

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