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Search: onr:"swepub:oai:lup.lub.lu.se:df945d81-df90-494d-896d-5aaf83acad49" > The Prognostic Effe...

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  • Ostergaard, AnnaPrincess Maxima Center for Pediatric Oncology/Hematology (author)

The Prognostic Effect of IKZF1 Deletions in ETV6:: RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia

  • Article/chapterEnglish2023

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  • 2023

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  • LIBRIS-ID:oai:lup.lub.lu.se:df945d81-df90-494d-896d-5aaf83acad49
  • https://lup.lub.lu.se/record/df945d81-df90-494d-896d-5aaf83acad49URI
  • https://doi.org/10.1097/HS9.0000000000000875DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152758226URI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • IKZF1 deletions are an established prognostic factor in childhood acute lymphoblastic leukemia (ALL). However, their relevance in patients with good risk genetics, namely ETV6::RUNX1 and high hyperdiploid (HeH), ALL remains unclear. We assessed the prognostic impact of IKZF1 deletions in 939 ETV6::RUNX1 and 968 HeH ALL patients by evaluating data from 16 trials from 9 study groups. Only 3% of ETV6::RUNX1 cases (n = 26) were IKZF1-deleted; this adversely affected survival combining all trials (5-year event-free survival [EFS], 79% versus 92%; P = 0.02). No relapses occurred among the 14 patients with an IKZF1 deletion treated on a minimal residual disease (MRD)-guided protocols. Nine percent of HeH cases (n = 85) had an IKZF1 deletion; this adversely affected survival in all trials (5-year EFS, 76% versus 89%; P = 0.006) and in MRD-guided protocols (73% versus 88%; P = 0.004). HeH cases with an IKZF1 deletion had significantly higher end of induction MRD values (P = 0.03). Multivariate Cox regression showed that IKZF1 deletions negatively affected survival independent of sex, age, and white blood cell count at diagnosis in HeH ALL (hazard ratio of relapse rate [95% confidence interval]: 2.48 [1.32-4.66]). There was no evidence to suggest that IKZF1 deletions affected outcome in the small number of ETV6::RUNX1 cases in MRD-guided protocols but that they are related to higher MRD values, higher relapse, and lower survival rates in HeH ALL. Future trials are needed to study whether stratifying by MRD is adequate for HeH patients or additional risk stratification is necessary.

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  • Enshaei, AmirUniversity of Newcastle upon Tyne (author)
  • Pieters, RobPrincess Maxima Center for Pediatric Oncology/Hematology (author)
  • Vora, AjayGreat Ormond Street Hospital (author)
  • Horstmann, Martin A.University Medical Center Hamburg-Eppendorf (author)
  • Escherich, GabrieleUniversity Medical Center Hamburg-Eppendorf (author)
  • Johansson, BertilLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Genetiska och epigenetiska studier av barnleukemi,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Genetic and epigenetic studies of pediatric leukemia,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kgen-bjo (author)
  • Heyman, MatsKarolinska Institutet,Karolinska Institute,Karolinska University Hospital (author)
  • Schmiegelow, KjeldCopenhagen University Hospital (author)
  • Hoogerbrugge, Peter M.Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Den Boer, Monique L.Oncode Institute,Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Kuiper, Roland P.University Medical Center Utrecht,Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Moorman, Anthony V.University of Newcastle upon Tyne (author)
  • Boer, Judith M.Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Van Leeuwen, Frank N.Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Princess Maxima Center for Pediatric Oncology/HematologyUniversity of Newcastle upon Tyne (creator_code:org_t)

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  • In:HemaSphere7:5, s. 875-8752572-9241

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