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Outcomes of CD19 chimeric antigen receptor T cell followed by haploidentical hematopoietic stem-cell transplantation in relapsed/refractory B-cell acute lymphoblastic leukemia with IKZF1 deletion

Bone Marrow Transplantation volume 57, pages 326–328 (2022)Cite this article

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Acute lymphoblastic leukemia (ALL) is a clinically and genetically heterogeneous hematopoietic malignancy, and 75% of ALL cases in adults are of B-cell lineage [1]. The Ikaros protein plays a vital role in lymphocyte differentiation and hematopoiesis. This transcription factor is mainly encoded and regulated by the IKZF1 gene [2], located in 7p12.2 and comprises of seven exons generating more than 10 isoforms through alternative splicing. Of the isoforms, IK1-3 is active and functional, while the IK4-10 isoform exerts a dominant-negative effect that impairs Ikaros’ normal function [3]. Further, IKZF1 deletion is associated with chemotherapy resistance and cancer relapse [4]. Numerous studies have depicted unfavorable clinical outcomes of IKZF1 deletion in children and adults with ALL and the management of treatment in ALL patients with IKZF1 deletion remain challenging and complicated.

In recent years, CD19-targeted Chimeric antigen receptor T (CAR-T) cell therapy has achieved significant milestones in R/R B-ALL. Despite high efficacy, post-CAR-T recurrence remains the main obstacle [5] and successive consolidation therapy following CD19 CAR-T cell treatment might be the optimal strategy to reduce recurrence rates and maintain CR status. Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is widely established as a potentially curative treatment for B-ALL patients. Interestingly, our previous research showed significant LFS and OS improvement in R/R ALL patients with pre-transplant minimal residual disease (MRD) negativity by employing haplo-HSCT after CAR-T treatment [6]. Here, we reported 11 patients with IKZF1-deleted R/R B-ALL, who were previously not responsive to chemotherapy or experienced rapid post-therapy disease relapse, who received CD19 CAR-T treatment at the Bone Marrow Transplantation Center, First Affiliated Hospital of Zhejiang University School of Medicine, from November 2016 to April 2021.

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Fig. 1: Clinical outcomes of 11 patients with IKZF1deletion after CAR-T cell therapy.

Data availability

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

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Acknowledgements

This work was supported by the National Natural Science Foundation of China under Grant [Nos. 82070179, 81970158]; Key Project of Science and Technology Department of Zhejiang Province under Grant [No. 2020C03G2013586].

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Authors and Affiliations

  1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Fang Ni, Elaine Tan Su Yin, Linghui Zhou, Houli Zhao, Yi Luo, Jimin Shi, Yongxian Hu & He Huang

  2. Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, China

    Fang Ni, Elaine Tan Su Yin, Linghui Zhou, Houli Zhao, Yi Luo, Jimin Shi, Yongxian Hu & He Huang

  3. Institute of Hematology, Zhejiang University, Hangzhou, China

    Fang Ni, Elaine Tan Su Yin, Linghui Zhou, Houli Zhao, Yi Luo, Jimin Shi, Yongxian Hu & He Huang

  4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China

    Fang Ni, Elaine Tan Su Yin, Linghui Zhou, Houli Zhao, Yi Luo, Jimin Shi, Yongxian Hu & He Huang

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  1. Fang Ni
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  2. Elaine Tan Su Yin
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Contributions

HH and YH designed the study, took care of the patients, and revised the manuscript. FN collected and analyzed clinical data, wrote and revised the paper. ET, LZ, HZ wrote and revised the manuscript. YL and JS provided clinical treatment to patients. All authors contributed to the article and approved the submitted paper.

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Correspondence to Yongxian Hu or He Huang.

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The authors declare no competing interests.

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Ni, F., Yin, E.T.S., Zhou, L. et al. Outcomes of CD19 chimeric antigen receptor T cell followed by haploidentical hematopoietic stem-cell transplantation in relapsed/refractory B-cell acute lymphoblastic leukemia with IKZF1 deletion. Bone Marrow Transplant 57, 326–328 (2022). https://doi.org/10.1038/s41409-021-01554-w

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