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Review
. 2022 Jan 27:11:790299.
doi: 10.3389/fonc.2021.790299. eCollection 2021.

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yishan Ye  1   2 , Luxin Yang  1   2 , Xiaolin Yuan  1   2 , He Huang  1   2 , Yi Luo  1   2
Affiliations
Review

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yishan Ye et al. Front Oncol. .

Abstract

Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection (e.g., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy.

Keywords: AML—acute myeloid leukemia; allogeneic hematopoietic cell transplantation; cell engineering; donor lymphocyte infusion (DLI); new drug.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Recommended strategies to optimize the donor lymphocyte infusion (DLI), including DLI regimen and protocol improvement, additional use of novel drugs, and cell engineering. The area within the dotted bordered square indicate strategies, including novel drugs and cell engineering. High-risk AML represents those defined to have a higher risk of relapse in different studies. cDLI, DLI prepared by leukapheresis of unstimulated peripheral blood; mDLI, DLI derived from peripheral blood stem cells mobilized by granulocyte colony-stimulating factor; HMAs, hypomethylating agents; FDC, full donor chimerism; CIK, cytokine-induced killer cells; TAA-T, tumor-antigen-specific T cells; FLAMSA, condition regimen including fludarabine, cytarabine, and amsacrine.
See this image and copyright information in PMC

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