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The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013.

Olsson, Linda LU ; Ivanov Öfverholm, Ingegerd; Norén-Nyström, Ulrika; Zachariadis, Vasilios; Nordlund, Jessica; Sjögren, Helene; Golovleva, Irina; Nordgren, Ann; Paulsson, Kajsa LU and Heyman, Mats, et al. (2015) In British Journal of Haematology 170(6). p.847-858
Abstract
Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (∆IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether ∆IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N = 218) or multiplex ligation-dependent probe amplification (N = 116) analyses. ∆IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P < 0·001)... (More)
Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (∆IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether ∆IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N = 218) or multiplex ligation-dependent probe amplification (N = 116) analyses. ∆IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P < 0·001) and overall survival (pOS; 73% vs. 89%; P = 0·001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, ∆IKZF1 was the strongest independent factor for relapse and death. ∆IKZF1 was present in 27% of cases with non-informative cytogenetics ('BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P < 0·001). Importantly, neither MRD nor WBC count predicted events in the ∆IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and ∆IKZF1 increased the risk of relapse (75% vs. 30% for cases with only ∆IKZF1; P = 0·045), indicating that BCP-other ALL with both P2RY8-CRLF2 and ∆IKZF1 constitutes a particularly high-risk group. (Less)
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British Journal of Haematology
volume
170
issue
6
pages
847 - 858
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:26018335
  • wos:000360757200012
  • scopus:84940582944
ISSN
0007-1048
DOI
10.1111/bjh.13514
language
English
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yes
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739ca956-4735-489c-bd39-0db57b0f7752 (old id 5441999)
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http://www.ncbi.nlm.nih.gov/pubmed/26018335?dopt=Abstract
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2015-06-06 12:19:19
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2017-11-19 03:19:09
@article{739ca956-4735-489c-bd39-0db57b0f7752,
  abstract     = {Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (∆IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether ∆IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N = 218) or multiplex ligation-dependent probe amplification (N = 116) analyses. ∆IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P &lt; 0·001) and overall survival (pOS; 73% vs. 89%; P = 0·001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, ∆IKZF1 was the strongest independent factor for relapse and death. ∆IKZF1 was present in 27% of cases with non-informative cytogenetics ('BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P &lt; 0·001). Importantly, neither MRD nor WBC count predicted events in the ∆IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and ∆IKZF1 increased the risk of relapse (75% vs. 30% for cases with only ∆IKZF1; P = 0·045), indicating that BCP-other ALL with both P2RY8-CRLF2 and ∆IKZF1 constitutes a particularly high-risk group.},
  author       = {Olsson, Linda and Ivanov Öfverholm, Ingegerd and Norén-Nyström, Ulrika and Zachariadis, Vasilios and Nordlund, Jessica and Sjögren, Helene and Golovleva, Irina and Nordgren, Ann and Paulsson, Kajsa and Heyman, Mats and Barbany, Gisela and Johansson, Bertil},
  issn         = {0007-1048},
  language     = {eng},
  number       = {6},
  pages        = {847--858},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013.},
  url          = {http://dx.doi.org/10.1111/bjh.13514},
  volume       = {170},
  year         = {2015},
}