Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia

BMC Cancer

Research Article

Qiu-Mei Yao¹  Yan-Rong Liu¹  Hao Jiang¹  Kai-Yan Liu¹  Bin Jiang¹  Guo-Rui Ruan¹  Qian Jiang¹  Lan-Ping Xu¹  Shan-Shan Chen¹  Xiao-Hui Zhang¹  Xiao-Jun Huang²  Mei-Jie Zhang³  Robert Peter Gale⁴ 

[1] 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;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;Division of Biostatistics, Medical College of Wisconsin, Milwaukee, USA;Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK;

关键词: IKZF1;    Acute lymphoblastic leukemia;    BCR-ABL1;    Chemotherapy;    Allotransplant;   

DOI  :  10.1186/s12885-016-2300-7

 received in 2015-07-02, accepted in 2016-04-01,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundInterrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia.MethodsOne 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.ResultsAmongst 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.ConclusionsIKZF1 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).

【 授权许可】

CC BY   
© Yao et al. 2016