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Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation

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Abstract

The prognosis of 11q23/KMT2A-rearranged (KMT2A-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important prognostic factor for relapse. Thus, we aimed to identify the evolution of KMT2A before and after allo-HSCT and the efficacy of preemptive immunotherapies for KMT2A-r AL patients receiving allo-HSCT. KMT2A expression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutive KMT2A-r AL patients. Pre-HSCT KMT2A positivity was correlated with post-HSCT KMT2A positivity (correlation coefficient=0.371, P<0.001). The rates of achieving KMT2A negativity after allo-HSCT were 96.6%, 92.9%, and 68.8% in the pre-HSCT low-level group (>0, <0.1%), intermediate-level group (≥ 0.1%, <1%), and high-level group (≥1%), respectively. The rates of regaining KMT2A positivity after allo-HSCT were 7.7%, 35.7%, 38.5%, and 45.5% for the pre-HSCT KMT2A-negative, low-level, intermediate-level, and high-level groups, respectively (P<0.001). The 4-year cumulative incidence of relapse after allo-HSCT was as high as 53.7% in the pre-HSCT KMT2A expression ≥ 0.1% group, which was compared to the KMT2A-negative group (15.1%) and KMT2A <0.1% group (31.2%). The clinical outcomes of patients with post-HSCT KMT2A positivity were poorer than those of patients with persistent KMT2A negativity. Although post-HSCT preemptive immunotherapies might help to achieve KMT2A negativity, the long-term efficacy was unsatisfactory. Thus, pre-HSCT KMT2A positivity was significantly associated with post-HSCT KMT2A positivity. The clinical outcomes of patients with post-HSCT KMT2A positivity were poor, which might not be overcome by commonly used immunotherapies.

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Funding

This work was supported by grants from the Capital’s Funds for Health Improvement and Research (2018-4-4089), Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation (BMU2020PY007), the Key Program of the National Natural Science Foundation of China (81930004), the National Key Research and Development Program of China (2017YFA0104500), the National Natural Science Foundation of China (81670175, 81870137 and 81900173), Innovative Research Groups of the National Natural Science Foundation of China (81621001), and CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-034), and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People’s Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Jing Liu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Yi-Fei Cheng, Ya-Zhen Qin, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Su Zhao & Xiao-Dong Mo

  2. Peking-Tsinghua Center for Life Sciences, Beijing, 100044, China

    Xiao-Jun Huang

  3. Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing, China

    Xiao-Jun Huang & Xiao-Dong Mo

  4. Collaborative Innovation Center of Hematology, Peking University, Beijing, China

    Xiao-Jun Huang & Xiao-Su Zhao

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  1. Jing Liu
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  2. Xiao-Hui Zhang
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Correspondence to Xiao-Su Zhao or Xiao-Dong Mo.

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Liu, J., Zhang, XH., Xu, LP. et al. Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation. Ann Hematol 100, 1267–1281 (2021). https://doi.org/10.1007/s00277-021-04488-x

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