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

Ostergaard, Anna ; Enshaei, Amir ; Pieters, Rob ; Vora, Ajay ; Horstmann, Martin A. ; Escherich, Gabriele ; Johansson, Bertil LU ; Heyman, Mats ; Schmiegelow, Kjeld and Hoogerbrugge, Peter M. , et al. (2023) In HemaSphere 7(5). p.875-875
Abstract

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;... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
HemaSphere
volume
7
issue
5
pages
875 - 875
publisher
Wolters Kluwer
external identifiers
  • pmid:37153875
  • scopus:85159360258
ISSN
2572-9241
DOI
10.1097/HS9.0000000000000875
language
English
LU publication?
yes
id
df945d81-df90-494d-896d-5aaf83acad49
date added to LUP
2023-08-10 13:06:38
date last changed
2024-04-20 00:19:56
@article{df945d81-df90-494d-896d-5aaf83acad49,
  abstract     = {{<p>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.</p>}},
  author       = {{Ostergaard, Anna and Enshaei, Amir and Pieters, Rob and Vora, Ajay and Horstmann, Martin A. and Escherich, Gabriele and Johansson, Bertil and Heyman, Mats and Schmiegelow, Kjeld and Hoogerbrugge, Peter M. and Den Boer, Monique L. and Kuiper, Roland P. and Moorman, Anthony V. and Boer, Judith M. and Van Leeuwen, Frank N.}},
  issn         = {{2572-9241}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  pages        = {{875--875}},
  publisher    = {{Wolters Kluwer}},
  series       = {{HemaSphere}},
  title        = {{The Prognostic Effect of IKZF1 Deletions in ETV6:: RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia}},
  url          = {{http://dx.doi.org/10.1097/HS9.0000000000000875}},
  doi          = {{10.1097/HS9.0000000000000875}},
  volume       = {{7}},
  year         = {{2023}},
}