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

doi:10.1007/s11684-018-0665-5

Front. Med.

2019, Vol. 13

Issue (3) : 354-364 https://doi.org/10.1007/s11684-018-0665-5

RESEARCH ARTICLE

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

Xiaodong Mo¹, Xiaohui Zhang¹, Lanping Xu¹, Yu Wang¹, Chenhua Yan¹, Huan Chen¹, Yuhong Chen¹, Wei Han¹, Fengrong Wang¹, Jingzhi Wang¹, Kaiyan Liu¹, Xiaojun Huang^1,²(

)

¹. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China
². Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100044, China

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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

Corresponding Author(s): Xiaojun Huang

Just Accepted Date: 20 December 2018 Online First Date: 25 January 2019 Issue Date: 05 June 2019

Cite this article:

Xiaodong Mo,Xiaohui Zhang,Lanping Xu, et al. Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation[J]. Front. Med., 2019, 13(3): 354-364.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0665-5
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I3/354

Fig.1 Diagram of patients enrolled. MRD-directed chemo-DLI was the first choice of patients in the MRD_co+ group and those who did not receive chemo-DLI because of patient or provider refusal to receive MRD-directed IFN-a treatment.

Tab.1 Patient characteristics between the IFN-a and chemo-DLI group

Fig.2 Cumulative incidence of relapse 2 years after MRD-directed immunotherapy according to (A) MRD status prior to immunotherapy: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 5.9% vs. 24.4%, P=0.241; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 5.9% vs. 21.4%, P=0.174; MRD_co+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 24.4% vs. 21.4%, P=0.833; and (B) MRD status after immunotherapy (12.9% vs. 27.3%, P=0.137).

Fig.3 Cumulative incidence of MRD-negative patients after immunotherapy. (A) 3 months: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 61.1% vs. 66.7%, P=0.611; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 61.1% vs. 42.9%, P=0.278; MRD_co+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 66.7% vs. 42.9%, P=0.260; (B) 2 years: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 83.3% vs. 86.7%, P=0.624; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 83.3% vs. 54.8%, P=0.064; MRD_co+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 86.7% vs. 54.8%, P=0.027.

Tab.2 Multivariate analysis of risk factors for the 2-year clinical outcomes after MRD-directed immunotherapy

Fig.4 Cumulative incidence of non-relapse mortality 2 years after MRD-directed immunotherapy according to (A) MRD status prior to immunotherapy: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 11.1% vs. 6.7%, P=0.664; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving Chemo-DLI: 11.1% vs. 0.0%, P=0.206; MRD_co+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 6.7% vs. 0.0%, P=0.335; and (B) MRD status after immunotherapy (2.8% vs. 18.2%, P=0.067).

Fig.5 Probability of disease-free survival 2 years after MRD-directed immunotherapy according to (A) MRD status prior to immunotherapy: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 83.0% vs. 68.9%, P=0.570; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 83.0% vs. 78.6%, P=0.649; MRD_co+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 68.9% vs. 78.6%, P=0.847; and (B) MRD status after immunotherapy (84.3% vs. 54.5%, P=0.006).

Fig.6 Probability of OS 2 years after MRD-directed immunotherapy according to (A) MRD status prior to immunotherapy: MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving IFN-a treatment: 83.0% vs. 85.6%, P=0.762; MRD_sin+ receiving IFN-a treatment vs. MRD_co+ receiving chemo-DLI: 83.0% vs. 84.6%, P=0.927; MRD_co+ receiving IFN-a v treatment s. MRD_co+ receiving chemo-DLI: 85.6% vs. 84.6%, P=0.849; and (B) MRD status after immunotherapy (91.2% vs. 60.6%, P=0.006).

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