Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Abstract

The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n=47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms’ tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377) and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P=0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.

Keywords

donor leukocyte infusion / hematopoietic stem cell transplantation / interferon-α / minimal residual disease / myelodysplastic syndrome

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Acknowledgements

The authors thank Editage for their English editing assistance as well as Drs. Daoxing Deng, Yujia Chi, and Wei Guo for their assistance in data collection. This work was supported by the Capital’s Funds for Health Improvement and Research (No. 2018-4-4089), the Key Program of the National Natural Science Foundation of China (No. 81530046), Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001), the Science and Technology Project of Guangdong Province of China (No. 2016B030230003), the National Science and Technology Support Program (No. 2014BAI09B13), and the Project of Health Collaborative Innovation of Guangzhou city (No. 201704020214).

Compliance with ethics guidelines

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, and Xiaojun Huang declare no potential financial conflict of interest related to this manuscript. Informed consent was obtained from all patients or their guardians. The study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Peking University People’s Hospital.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/ 10.1007/s11684-018-0665-5 and is accessible for authorized users.

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