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Acute Leukemia

Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL

Bone Marrow Transplantation volume 50, pages 354–362 (2015)Cite this article

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Abstract

We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.

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Acknowledgements

This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120175). Statistical analyses performed in this article were advised by the Catholic Medical Center Clinical Research Coordinating Center.

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  1. Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

    M Kim, J Park, Y Kim & K Han

  2. Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea

    D-W Kim, Y-J Kim, Y-W Jeon, J-H Yoon, S-H Shin, S-A Yahng, S-E Lee, B-S Cho, K-S Eom, H-J Kim, C-Ki Min, S-G Cho, J-W Lee, W-S Min & S Lee

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Kim, M., Park, J., Kim, DW. et al. Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL. Bone Marrow Transplant 50, 354–362 (2015). https://doi.org/10.1038/bmt.2014.281

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