Clinical effect of donor-derived natural killer cell infusion (DNKI) after HLA-haploidentical hematopoietic cell transplantation (HCT) was evaluated in high-risk myeloid malignancy in phase 2, randomized trial. Seventy-six evaluable patients (aged 21–70 years) were randomized to receive DNKI (N = 40) or not (N = 36) after haploidentical HCT. For the HCT conditioning, busulfan, fludarabine, and anti-thymocyte globulin were administered. DNKI was given twice 13 and 20 days after HCT. Four patients in the DNKI group failed to receive DNKI. In the remaining 36 patients, median DNKI doses were 1.0 × 108/kg and 1.4 × 108/kg on days 13 and 20, respectively. Intention-to-treat analysis showed a lower disease progression for the DNKI group (30-month cumulative incidence, 35% vs 61%, P = 0.040; subdistribution hazard ratio, 0.50). Furthermore, at 3 months after HCT, the DNKI patients showed a 1.8- and 2.6-fold higher median absolute blood count of NK and T cells, respectively. scRNA-sequencing analysis in seven study patients showed that there was a marked increase in memory-like NK cells in DNKI patients which, in turn, expanded the CD8+ effector-memory T cells. In high-risk myeloid malignancy, DNKI after haploidentical HCT reduced disease progression. This enhanced graft-vs-leukemia effect may be related to the DNKI-induced, post-HCT expansion of NK and T cells. Clinical trial number: NCT02477787.
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For the patient-level data generated in the study, please contact Dr. Kyoo-Hyung Lee at email@example.com.
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The authors thank Drs. Koen van Besien (Weill Cornell Medicine) and Haesook Teresa Kim (Dana-Farber Cancer Institute) for their critical review of the manuscript and invaluable comments. This work was supported by grants from the following bodies: 1. Korean Health Technology R&D Project, Ministry of Health and Welfare (A121934, HI12C1788), Republic of Korea. 2. R&D Convergence Program of the National Research Council of Science & Technology (NST) (CRC-15-02-KRIBB), Republic of Korea. 3. National Research Foundation of Korea (NRF) (2019R1A2C3002034, 2019R1A2C1007906, 2020R1A2C2012467, 2020R1A2B5B03094920, and 2021M3A9I4024447), Republic of Korea. 4. Electronics and Telecommunications Research Institute (ETRI) grant (22RB1100, Exploratory and Strategic Research of ETRI-KAIST ICT Future Technology), Republic of Korea. 5. Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM 5502221), Republic of Korea.
K-HL, E-JC, J-HL, J-HL, and H-SP are recipients of royalty from Ingenium Therapeutics, Daejon, Korea. K-HL and E-JC are consultants for the same company and receive consultation fees. The other authors declare no competing conflict of interest.
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Lee, KH., Yoon, S.R., Gong, JR. et al. The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial. Leukemia (2023). https://doi.org/10.1038/s41375-023-01849-5