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Lookup NU author(s): Professor Anthony MoormanORCiD, Jude Gibson, Melvin JoyORCiD, Dr Amir EnshaeiORCiD, Professor Christine Harrison
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Background: High risk genetic abnormalities (HRG) in children and young adults diagnosed with acute lymphoblastic leukaemia (ALL) are well established and important for treatment stratification. Collectively, they account for 10-15% patients but are individually rare and frequently grouped together for risk stratification and analysis.Aims: To determine the outcome of patients with HRG treated on consecutive clinical trials both collectively and individually. To identify additional risk factors associated with specific HRG.Methods: We analysed individual patient data from 615 patients treated on or according to four consecutive treatment protocols: UKALLXI (n=67), UKALL97 (n=153), UKALL2003 (n=226), UKALL2011 (n=169). The cohort comprised KMT2A rearrangements (n=202), iAMP21 (n=164), BCR::ABL1 (n=75), ABL-class fusions (n=58), low hypodiploidy (LH, n=47), near haploid (NH, n=43), MYC rearrangements (n=14) and TCF3::HLF (n=12). None of the patients with BCR::ABL1 or an ABL-fusion in this cohort received a tyrosine kinase inhibitor in frontline therapy. Over the course of these four protocols trial eligibility, risk stratification criteria and routine screening changed. Hence the relative frequency of the abnormalities are not representative. Survival rates are quoted at 5 years with 95% confidence interval (CI).Results: Between 1990 and 2021 an increasing number of genetic abnormalities were treated as high-risk driving an increase in survival (OS) for patients with HRG from 47% (35-59) to 84% (77-89), p<0.001. Although treatment evolved considerably over this period, we noted a decrease in relapse rate (RR) for patients with HRG treated on ALL97/99, UKALL2003 and UKALL2011 who were allocated to the high-risk arm (regimen C) compared to those who were not treated as high-risk [47% (36-60) to 28% (24-33), p<0.01]. Analysis by individual abnormality showed clear evidence of improved outcome for patients with KMT2A-r or iAMP21 but the RR for patients with NH and LH remained high. In the whole cohort and within each protocol there was evidence of outcome heterogeneity by individual genetic abnormality with NH, MYC-r and TCF3::HLF having higher RR compared with KMT2A-r and iAMP21. Analysis of risk factors per abnormality revealed important observations. Among KMT2A-r cases, risk factors for RR included CNS disease (positive 68% v negative 29%, p<0.01) and immunophenotype (B-cell 35% v T-cell 7%, p<0.01) but not age, partner gene or end of induction measurable residual disease (EOI MRD). Similarly, the RR for ABL-class fusion patients varied by immunophenotype [T-cell 10% (1-53) v B-cell 52% (37-68), p=0.03]. We did not observe any risk factors among patients with iAMP21 or NH. Among LH patients, male sex and EOI MRD were associated with inferior outcomes but the number of cases was modest. For both the NH and LH groups, we examined outcome according to the presence and absence of a masked clone. This was not prognostic among NH cases. However, LH patients with both clones visible had an inferior OS compared to LH cases where only one clone was detected (36% (11-63) v 79% (47-93) / 77% (54-90), p=0.01]. This difference could not be explained by changes in cytogenetic analysis over this period.Summary/Conclusion: The outcome of patients with ALL and HRG has improved over the past three decades largely due to treating treatment stratification. Among most patients with HRG, age and EOI MRD were not strong predictors of outcome. The presence of HRG in T-ALL may confer a differential prognostic effect.
Author(s): Moorman A, Gibson J, Joy M, Kirkwood A, Lawson A, Kearns P, Moppett J, Samarasinghe S, Vora A, Enshaei A, Harrison C
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: 31st Congress of the European Hematology Association (EHA2026)
Year of Conference: 2026
Pages: 1-2
Online publication date: 10/06/2026
Acceptance date: 24/04/2026
Date deposited: 25/06/2026
ISSN: 2572-9241
Publisher: HemaSphere
URL: https://doi.org/10.1002/hem3.70420
DOI: 10.1002/hem3.70420
Notes: Abstract number PF336
Library holdings: Search Newcastle University Library for this item
Series Title: EHA2026 Annual Congress Edition June 2026
ISBN: 25729241
