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Allogeneic hematopoietic stem cell transplantation overcome the poor prognosis of patients with IKZF1plus CD20–a very high-risk subtype in B-cell acute lymphoblastic leukemia

Abstract

Genetic deletions of IKZF1 (IKZF1del) and IKZF1del plus other mutations (IKZF1plus) have been identified in B-cell acute lymphoblastic leukemia (B-ALL) with a poor prognosis. Herein, we investigated the combination of IKZF1del and CD20 immunotypes in adult patients with B-ALL in the PDT-ALL-2016 cohort. This study cohort consisted of 161 patients with B-ALL with detailed information on IKZF1del and CD20 expression. The independent cohort included 196 patients from the TARGET dataset. IKZF1del was detected in 36.0% of patients with 3-year event-free survival (EFS) of 37.1 ± 6.7% and overall survival (OS) of 51.5 ± 7.3%, compared to IKZF1 wild-type (IKZF1wt) with an EFS 55.3 ± 5.1% (P = 0.011) and OS 74.4 ± 4.5% (P = 0.013), respectively. CD20-positive (CD20+) was associated with inferior EFS compared to the CD20-negative (CD20-) group (P = 0.020). Furthermore, IKZF1del coupled with CD20+, IKZF1del/CD20+, comprised 12.4% of patients with a 3-year EFS of 25.0 ± 9.7%, compared with IKZF1wt/CD20 (P ≤ 0.001) and IKZF1del/CD20 (P = 0.047) groups. Multivariable analyses demonstrated the independence of IKZF1del/CD20+, with the highest predicted hazard ratio for EFS and OS. Furthermore, the prognostic panel of IKZF1del/CD20+ was confirmed in the TARGET cohort. Notably, neither the IKZF1del, CD20+, or IKZF1del/CD20+ groups were identified to have poor outcomes in the cohort of allogeneic hematopoietic stem cell transplantation (n = 81).Collectively, our data define IKZF1del/CD20+ as a very high-risk subtype in B-ALL, and allo-HSCT could abrogate the poor outcome of both IKZF1del and IKZF1del/CD20+ subsets.

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Fig. 1: Flow diagram of patients in trial.
Fig. 2: Kaplan–Meier analysis of 3-year EFS and OS rate between IKZF1del/CD20+ subgroup and other subgroups.
Fig. 3: Kaplan–Meier analysis of 3-year EFS and OS rate between IKZF1del/CD20 + subgroup and other subgroups in transplantation cohort (n = 81).

Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (NSFC 82170163, 81970147, 81770170, to HSZ), the Science and Technology Planning Project of Guangdong Province (No. 2017A030313601 to HSZ), the Clinical Trial Funding of SMU (2016A020215112), and Nanfang Hospital (LC2016ZD009/2019CR012).

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Contributions

TBQ and ZHS contributed to the concept and design of this research. TBQ, CZH and LDN brewed and collected data. WZX, LQL and HXJ performed the statistical analyses and LXJ, HKY collected and analyzed the data of other independent cohort. LXL, SJ, XN and LQF commented critically on an advanced manuscript version regarding the interpretation of the results and the discussion. LR, ZX, HF and FZP offered material support and revised the paper. LQF and ZHS accessed the funding of research. TBQ drafted the manuscript. All authors read and approved the final version of the manuscript. TBQ, CZH. and WZX are co-first authors. The data that support the findings of this study are available from the corresponding author upon request.

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Correspondence to Qifa Liu or Hongsheng Zhou.

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The authors declare no competing interests.

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The study was performed in accordance with the Declaration of Helsinki, and the protocol was approved by ethical review boards of Southern Hospital, Southern Medical University before study initiation(NFEC-2018-002).

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Tang, B., Cai, Z., Wang, Z. et al. Allogeneic hematopoietic stem cell transplantation overcome the poor prognosis of patients with IKZF1plus CD20–a very high-risk subtype in B-cell acute lymphoblastic leukemia. Bone Marrow Transplant 57, 1751–1757 (2022). https://doi.org/10.1038/s41409-022-01797-1

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