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Prophylactic modified donor lymphocyte infusion after low-dose ATG-F-based haploidentical HSCT with myeloablative conditioning in high-risk acute leukemia: a matched-pair analysis

Bone Marrow Transplantation volume 56, pages 664–672 (2021)Cite this article

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Abstract

Both haploidentical hematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) exhibit strong graft-versus-leukemia (GVL) effect. However, the role of prophylactic DLI following haploidentical HSCT remains unclear. Here, 34 patients with high-risk acute leukemia who underwent low-dose anti-T-lymphocyte globulin-Fresenius (ATG-F)-based myeloablative haploidentical HSCT and prophylactic modified DLI (pro-DLI) were well-matched with patients without pro-DLI. The 5-year overall survival (OS) (67.8% versus 41.3%, P < 0.01) and leukemia-free survival (LFS) (64.6% versus 33.9%, P < 0.01) of pro-DLI cohort were superior to the control cohort. A slightly higher GVHD-free/relapse-free survival was found in the pro-DLI cohort (32.8% versus 16.3%, P = 0.32). The 5-year cumulative incidence of relapse of the pro-DLI recipients was significantly lower than that of the control cohort (14.7% versus 49.3%, P = 0.01). The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days after pro-DLI was 17.6% and 9.1%, respectively. There was no difference between the two cohorts in terms of the cumulative incidence of chronic GVHD and non-relapse mortality. Data from the multivariate analysis demonstrated that pro-DLI was an independent protective variable for LFS (P = 0.01, hazard ratio {HR} = 0.35), OS (P = 0.01, HR = 0.32), and relapse (P = 0.02, HR = 0.33). Taken together, we demonstrate that pro-DLI after ATG-F-based HSCT effectively decreases the risk of relapse and improves long-term survival of patients with high-risk acute leukemia without increasing treatment toxicity.

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Fig. 1: Diagram of prophylactic modified donor lymphocyte infusion and matched-pair analysis.
Fig. 2: Cumulative incidence of GVHD.
Fig. 3: Cumulative incidence of relapse and NRM.
Fig. 4: Survival.

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Acknowledgements

This work was supported by grants from The National Key Research and Development Program of China [grant number 2018YFA0107804], The National Natural Science Foundation of China [grant numbers 81970158] and Zhejiang Natural Science Foundation [grant numbers LY18H080001].

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  1. These authors contributed equally: He Huang, Yi Luo

Authors and Affiliations

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

    Luxin Yang, Yamin Tan, Jimin Shi, Yanmin Zhao, Jian Yu, Yongxian Hu, Xiaoyu Lai, Yang Yang, He Huang & Yi Luo

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

    Luxin Yang, Yamin Tan, Jimin Shi, Yanmin Zhao, Jian Yu, Yongxian Hu, Xiaoyu Lai, Yang Yang, He Huang & Yi Luo

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Yang, L., Tan, Y., Shi, J. et al. Prophylactic modified donor lymphocyte infusion after low-dose ATG-F-based haploidentical HSCT with myeloablative conditioning in high-risk acute leukemia: a matched-pair analysis. Bone Marrow Transplant 56, 664–672 (2021). https://doi.org/10.1038/s41409-020-01088-7

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