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ACUTE MYELOID LEUKEMIA

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 volume 37, pages 807–819 (2023)Cite this article

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Abstract

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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Fig. 1: Treatment schema and random allocation of the patients.
Fig. 2: HCT outcomes in each treatment group determined by intention-to-treat analysis.
Fig. 3: Subgroup analysis for disease progression and NK and T cell recovery after haploidentical HCT with or without post-HCT DNKI infusion.
Fig. 4: Single cellular landscape of PBMCs after haploidentical hematopoietic cell transplantation (HCT) with or without post-transplantation donor natural killer cell infusion (DNKI).
Fig. 5: Donor natural killer cell infusion (DNKI) expands memory-like NK cells, which, in turn clonally expand CD8+ effector-memory T cells.

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Data availability

For the patient-level data generated in the study, please contact Dr. Kyoo-Hyung Lee at haploset@gmail.com.

References

  1. Brissot E, Labopin M, Ehninger G, Stelljes M, Brecht A, Ganser A, et al. Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: a report on 1578 patients from the Acute Leukemia Working Party of the EBMT. Haematologica. 2019;104:524–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Deeg HJ, Scott BL, Fang M, Shulman HM, Gyurkocza B, Myerson D, et al. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood. 2012;120:1398–408.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Lee KH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, et al. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011;118:2609–17.

    CAS  PubMed  Google Scholar 

  4. Fuchs EJ, O’Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137:420–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Herberman RB, Nunn ME, Holden HT, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer. 1975;16:230–9.

    CAS  PubMed  Google Scholar 

  6. Kiessling R, Klein E, Pross H, Wigzell H. “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol. 1975;5:117–21.

    CAS  PubMed  Google Scholar 

  7. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–10.

    CAS  PubMed  Google Scholar 

  8. Chiossone L, Dumas PY, Vienne M, Vivier E. Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol. 2018;18:671–88.

    CAS  PubMed  Google Scholar 

  9. Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105:4878–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Miller JS, Cooley S, Parham P, Farag SS, Verneris MR, McQueen KL, et al. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood. 2007;109:5058–61.

    CAS  PubMed Central  Google Scholar 

  11. Lundqvist A, Philip McCoy J, Samsel L, Childs R. Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors. Blood. 2007;109:3603–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.

    CAS  PubMed  Google Scholar 

  13. Song Y, Hu B, Liu Y, Jin Z, Zhang Y, Lin D, et al. IL-12/IL-18-preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation. Eur J Immunol. 2018;48:670–82.

    CAS  PubMed  Google Scholar 

  14. Huber CM, Doisne JM, Colucci F. IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation. Eur J Immunol. 2015;45:1727–35.

    PubMed  PubMed Central  Google Scholar 

  15. Ciurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, et al. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022;36:155–64.

    CAS  PubMed  Google Scholar 

  16. Berrien-Elliott MM, Foltz JA, Russler-Germain DA, Neal CC, Tran J, Gang M, et al. Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Sci Transl Med. 2022;14:eabm1375.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Devillier R, Calmels B, Guia S, Taha M, Fauriat C, Mfarrej B, et al. Phase I trial of prophylactic donor-derived IL-2-activated NK cell infusion after allogeneic hematopoietic stem cell transplantation from a matched sibling donor. Cancers. 2021;13:2673.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K, Willis D, et al. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood. 2017;130:1857–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Jaiswal SR, Zaman S, Nedunchezhian M, Chakrabarti A, Bhakuni P, Ahmed M, et al. CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: a pilot study. Cytotherapy. 2017;19:531–42.

    CAS  PubMed  Google Scholar 

  20. Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Kang YL, et al. Donor-derived natural killer cell infusion after human leukocyte antigen-haploidentical hematopoietic cell transplantation in patients with refractory acute leukemia. Biol Blood Marrow Transpl. 2016;22:2065–76.

    CAS  Google Scholar 

  21. Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, et al. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transpl. 2014;20:696–704.

    CAS  Google Scholar 

  22. Stern M, Passweg JR, Meyer-Monard S, Esser R, Tonn T, Soerensen J, et al. Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transpl. 2013;48:433–8.

    CAS  Google Scholar 

  23. Brehm C, Huenecke S, Quaiser A, Esser R, Bremm M, Kloess S, et al. IL-2 stimulated but not unstimulated NK cells induce selective disappearance of peripheral blood cells: concomitant results to a phase I/II study. PLoS One. 2011;6:e27351.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Rizzieri DA, Storms R, Chen DF, Long G, Yang Y, Nikcevich DA, et al. Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2010;16:1107–14.

    Google Scholar 

  25. Yoon SR, Lee YS, Yang SH, Ahn KH, Lee JH, Lee JH, et al. Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study. Bone Marrow Transplant. 2010;45:1038–46.

    CAS  PubMed  Google Scholar 

  26. Shah NN, Baird K, Delbrook CP, Fleisher TA, Kohler ME, Rampertaap S, et al. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation. Blood. 2015;125:784–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fehniger TA, Miller JS, Stuart RK, Cooley S, Salhotra A, Curtsinger J, et al. A Phase 1 trial of CNDO-109-activated natural killer cells in patients with high-risk acute myeloid leukemia. Biol Blood Marrow Transpl. 2018;24:1581–9.

    CAS  Google Scholar 

  28. Bachanova V, Sarhan D, DeFor TE, Cooley S, Panoskaltsis-Mortari A, Blazar BR, et al. Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother. 2018;67:483–94.

    CAS  PubMed  Google Scholar 

  29. Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8:357ra123.

    PubMed  PubMed Central  Google Scholar 

  30. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105:3051–7.

    CAS  PubMed  Google Scholar 

  31. Yang Y, Lim O, Kim TM, Ahn YO, Choi H, Chung H, et al. Phase I study of random healthy donor-derived allogeneic natural killer cell therapy in patients with malignant lymphoma or advanced solid tumors. Cancer Immunol Res. 2016;4:215–24.

    CAS  PubMed  Google Scholar 

  32. Szmania S, Lapteva N, Garg T, Greenway A, Lingo J, Nair B, et al. Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients. J Immunother. 2015;38:24–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Wagner J, Pfannenstiel V, Waldmann A, Bergs JWJ, Brill B, Huenecke S, et al. A two-phase expansion protocol combining interleukin (IL)-15 and IL-21 improves natural killer cell proliferation and cytotoxicity against rhabdomyosarcoma. Front Immunol. 2017;8:676.

    PubMed  PubMed Central  Google Scholar 

  34. Fehniger TA, Shah MH, Turner MJ, VanDeusen JB, Whitman SP, Cooper MA, et al. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol. 1999;162:4511–20.

    CAS  PubMed  Google Scholar 

  35. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.

    CAS  PubMed  Google Scholar 

  36. Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N. Heterogeneous clearance of antithymocyte globulin after CD34+-selected allogeneic hematopoietic progenitor cell transplantation. Biol Blood Marrow Transpl. 2005;11:609–18.

    Google Scholar 

  37. Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell 2021;184:3573–87.e29.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Bi J, Tian Z. NK cell exhaustion. Front Immunol. 2017;8:760.

    PubMed  PubMed Central  Google Scholar 

  39. Song L, Cohen D, Ouyang Z, Cao Y, Hu X, Liu XS. TRUST4: immune repertoire reconstruction from bulk and single-cell RNA-seq data. Nat Methods. 2021;18:627–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Browaeys R, Saelens W, Saeys Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2020;17:159–62.

    CAS  PubMed  Google Scholar 

  41. Braun M, Aguilera AR, Sundarrajan A, Corvino D, Stannard K, Krumeich S, et al. CD155 on tumor cells drives resistance to immunotherapy by inducing the degradation of the activating receptor CD226 in CD8(+) T Cells. Immunity. 2020;53:805–23.e15.

    CAS  PubMed  Google Scholar 

  42. Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, et al. Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat Genet. 2016;48:838–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Cao J, Spielmann M, Qiu X, Huang X, Ibrahim DM, Hill AJ, et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature. 2019;566:496–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kallies A, Carotta S, Huntington ND, Bernard NJ, Tarlinton DM, Smyth MJ, et al. A role for Blimp1 in the transcriptional network controlling natural killer cell maturation. Blood. 2011;117:1869–79.

    CAS  PubMed  Google Scholar 

  45. Gordon SM, Chaix J, Rupp LJ, Wu J, Madera S, Sun JC, et al. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity. 2012;36:55–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Cooper MA. Natural killer cells might adapt their inhibitory receptors for memory. Proc Natl Acad Sci USA. 2018;115:11357–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Berrien-Elliott MM, Cashen AF, Cubitt CC, Neal CC, Wong P, Wagner JA, et al. Multidimensional analyses of donor memory-like NK cells reveal new associations with response after adoptive immunotherapy for leukemia. Cancer Discov. 2020;10:1854–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Martin MD, Badovinac VP. Defining memory CD8 T cell. Front Immunol. 2018;9:2692.

    PubMed  PubMed Central  Google Scholar 

  49. Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102:401–10.

    PubMed  PubMed Central  Google Scholar 

  50. Leung W, Iyengar R, Turner V, Lang P, Bader P, Conn P, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172:644–50.

    CAS  PubMed  Google Scholar 

  51. Cooley S, Trachtenberg E, Bergemann TL, Saeteurn K, Klein J, Le CT, et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009;113:726–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Storek J, Mohty M, Boelens JJ. Rabbit anti-T cell globulin in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2015;21:959–70.

    CAS  Google Scholar 

  53. Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel LM, Podgorny P, et al. Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Cytotherapy. 2012;14:1258–75.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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.

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  1. These authors contributed equally: Kyoo-Hyung Lee, Suk Ran Yoon, Jeong-Ryeol Gong.

Authors and Affiliations

  1. Hematology Section, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Kyoo-Hyung Lee, Eun-Ji Choi, Je-Hwan Lee, Jung-Hee Lee, Yunsuk Choi, Han-Seung Park, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Jimin Woo, Hyeran Kang, Seunghyun Baek & Su Mi Kim

  2. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

    Suk Ran Yoon, Soo-Yeon Park, Sol-Ji Jung, Hanna Kim, Soo Yun Lee, Haiyoung Jung, Jae-Eun Byun & Inpyo Choi

  3. Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea

    Suk Ran Yoon, Haiyoung Jung, Mirang Kim, Seon-Young Kim, Jeong-Hwan Kim & Inpyo Choi

  4. Department of Bio and Brain Engineering, Laboratory for Systems Biology and Bio-Inspired Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea

    Jeong-Ryeol Gong, Hoon-Min Kim & Kwang-Hyun Cho

  5. Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Hun Sik Kim

  6. Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Chan-Jeoung Park

  7. Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Sung-Cheol Yun

  8. Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju, Republic of Korea

    Jae-Eun Byun

  9. Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

    Mirang Kim, Seon-Young Kim & Jeong-Hwan Kim

  10. Ingenium Therapeutics, Daejeon, Republic of Korea

    Inpyo Choi

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Contributions

K-HL: Conceptualization, resources, study design, project administration, supervision, manuscript writing, and editing. SRY: NK cell production, analytical experiments, and data analysis. J-RG: Single-cell RNA analysis, manuscript writing and editing. E-JC: Study patient reenrollment and care, data analysis, statistical analysis, and manuscript editing. HSK: FACS data analysis. C-JP: FACS data analysis. S-CY: Statistical consultation and analysis. S-YP: NK cell production, analytical experiments, and data analysis. S-JJ: NK cell production, analytical experiments, and data analysis. HK: NK cell production, analytical experiments, and data analysis. SYL: NK cell production, analytical experiments, and data analysis. HJ: Single-cell RNA analysis and data interpretation. J-EB: Single-cell RNA analysis and data interpretation. MK: Single-cell RNA analysis and data interpretation. S-YK: Single-cell RNA analysis and data interpretation. J-HK: Single-cell RNA analysis and data interpretation. J-HL: Study patient enrollment and care, clinical data interpretation, and data analysis. J-HL: Clinical data analysis and interpretation. YC: Clinical data analysis and interpretation. H-SP: Patient management, clinical data interpretation, and data analysis. Y-SL: HCT management and clinical study data management. Y-AK: HCT management and clinical study data management. MJ: HCT management and clinical data management. JMW: HCT management and clinical data management. HK: HCT management and clinical data management. SB: HCT management and study data management. SMK: HCT management and study data management. H-MK: Single-cell RNA analysis, manuscript writing and editing. K-HC: Study design, resources, supervision, single-cell RNA analysis, manuscript writing and editing. IC: Conceptualization, resources, study design, project administration, supervision, manuscript writing, and editing.

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Correspondence to Kyoo-Hyung Lee, Kwang-Hyun Cho or Inpyo Choi.

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Competing interests

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 37, 807–819 (2023). https://doi.org/10.1038/s41375-023-01849-5

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