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- Title
Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia.
- Authors
Qiu-Mei Yao; Kai-Yan Liu; Gale, Robert Peter; Bin Jiang; Yan-Rong Liu; Qian Jiang; Hao Jiang; Xiao-Hui Zhang; Mei-Jie Zhang; Shan-Shan Chen; Xiao-Jun Huang; Lan-Ping Xu; Guo-Rui Ruan; Yao, Qiu-Mei; Liu, Kai-Yan; Jiang, Bin; Liu, Yan-Rong; Jiang, Qian; Jiang, Hao; Zhang, Xiao-Hui
- Abstract
<bold>Background: </bold>Interrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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).
- Subjects
LYMPHOBLASTIC leukemia; DIFFUSE large B-cell lymphomas; PROTEIN-tyrosine kinases; CANCER chemotherapy; POLYMERASE chain reaction; LYMPHOBLASTIC leukemia treatment; B cells; HOMOGRAFTS; GENETIC mutation; PROGNOSIS; PROTEINS; TRANSPLANTATION of organs, tissues, etc.
- Publication
BMC Cancer, 2016, Vol 16, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-016-2300-7