The clinical impact of IKZF 1 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

Paediatric B‐cell precursor acute lymphoblastic leukaemias ( BCP ALL ) with IKZF 1 deletions (∆ IKZF 1 ) are associated with a poor outcome. However, there are conflicting data as to whether ∆ IKZF 1 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 IKZF 1 status based on either single nucleotide polymorphism array ( N = 218) or multiplex ligation‐dependent probe amplification ( N = 116) analyses. ∆ IKZF 1 , 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 , ∆ IKZF 1 was the strongest independent factor for relapse and death. ∆ IKZF 1 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 ∆ IKZF 1 ‐positive cases. Co‐occurrence of pseudoautosomal region 1 ( PAR 1) deletions in Xp22.33/Yp11.32 ( P2 RY 8 ‐ CRLF 2 ) and ∆ IKZF 1 increased the risk of relapse (75% vs. 30% for cases with only ∆ IKZF 1 ; P = 0·045), indicating that BCP ‐other ALL with both P2 RY 8 ‐ CRLF 2 and ∆ IKZF 1 constitutes a particularly high‐risk group.