title: Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  Interrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia.
  
  
  METHODS
  One hundred sixty-five consecutive adults with common B-cell ALL were tested for IKZF1 deletion and for BCR/ABL. Deletions in IKZF1 were detected using multiplex RQ-PCR, multiplex fluorescent PCR, sequence analysis and multiplex ligation-dependent probe amplification (MLPA). BCR/ABL was detected using RQ-PCR. All subjects received chemotherapy and some also received an allotransplant and tyrosine kinase-inhibitors. Multivariate analyses were done to identify associations between IKZF1 deletion and other variables on non-relapse mortality (NRM), cumulative incidence of relapse (CIR), leukemia-free survival (LFS) and survival.
  
  
  RESULTS
  Amongst subjects achieving complete remission those with IKZF1 deletion had similar 5-year non-relapse mortality (NRM) (11% [2-20%] vs. 16% [4-28%]; P = 0.736), a higher 5-year cumulative incidence of relapse (CIR) (55% [35-76%] vs. 25% [12-38%]; P = 0.004), and worse 5-year leukemia-free survival (LFS) (33% [16-52%] vs. 59% [42-73%]; P = 0.012) and survival (48% [33-62%] vs. 75% [57-86%]; P = 0.002). In multivariate analyses IKZF1 deletion was associated with an increased relapse (relative risk [RR] =2.7, [1.4-5.2]; P = 0.002), a higher risk of treatment-failure (inverse of LFS; RR = 2.1, [1.2-3.6]; P = 0.007) and a higher risk of death (RR = 2.8, [1.5-5.5]; P = 0.002). The adverse impact of IKZF1 deletion on outcomes was stronger in subjects without vs. with BCR-ABL1 and in subjects receiving chemotherapy-only vs. an allotransplant.
  
  
  CONCLUSIONS
  IKZF1 deletion was independently-associated with a higher relapse risk and worse LFS and survival in adults with common B-cell ALL after adjusting for other prognostic variables and differences in therapies. These data suggest IKZF1 deletion may be a useful prognostic variable in adults with common B-cell ALL, especially in persons without BCR-ABL1 and those receiving chemotherapy-only. Transplants appear to overcome the adverse impact of IKZF1 deletion on therapy-outcomes but confirmation in a randomized study is needed. The trial was registered in 2007 with the Beijing Municipal Government (Beijing Municipal Health Bureau Registration N: 2007-1007).
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Qiu-Mei
authors.initials: QM
authors.lastname: Yao
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China. lpxu_0415@sina.com.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China. ruanguorui@pkuph.edu.cn.
authors.forename: Guo-Rui
authors.initials: GR
authors.lastname: Ruan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology / Q000637:transplantation; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D017384:Sequence Deletion; D014184:Transplantation, Homologous
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor; D016044:Fusion Proteins, bcr-abl
keywords: Acute lymphoblastic leukemia; Allotransplant; BCR-ABL1; Chemotherapy; IKZF1