Faculty Collaboration Database

Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia. BMC Cancer 2016 Apr 11;16:269

Date

04/14/2016

Pubmed ID

27067989

Pubmed Central ID

PMC4828764

DOI

10.1186/s12885-016-2300-7

Scopus ID

2-s2.0-84963553771 (requires institutional sign-in at Scopus site)   30 Citations

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).

Author List

Yao QM, Liu KY, Gale RP, Jiang B, Liu YR, Jiang Q, Jiang H, Zhang XH, Zhang MJ, Chen SS, Huang XJ, Xu LP, Ruan GR

Author

Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
B-Lymphocytes
Disease-Free Survival
Female
Fusion Proteins, bcr-abl
Humans
Ikaros Transcription Factor
Male
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Sequence Deletion
Transplantation, Homologous