4.7 Article

Decrease post-transplant relapse using donor-derived expanded NK-cells

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LEUKEMIA
卷 36, 期 1, 页码 155-164

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SPRINGERNATURE
DOI: 10.1038/s41375-021-01349-4

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资金

  1. National Institutes of Health, National Cancer Institute [P30 CA016672, P01 CA49639]
  2. Leukemia & Lymphoma Society Translational Research Program Award [6149-14]
  3. Cancer Prevention Research Institute of Texas [RP110553]
  4. University of Texas MD Anderson Cancer Center AML Moonshot Program
  5. University of Texas MD Anderson Cancer Center High Impact Clinical Research Support Program
  6. McKee Family Foundation
  7. Taylor Trudeau Cycle for Life Charitable Foundation

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In this phase I/II clinical trial, high doses of mb-IL21 ex vivo expanded donor-derived NK cells were administered to 25 patients with myeloid malignancies undergoing haploidentical stem-cell transplantation. The results showed a significant decrease in the relapse rate and improved disease-free survival compared to the control group, with a particular benefit in patients without donor-specific anti-HLA antibodies. The administration of expanded NK cells post-transplantation was safe and led to NK cell-dominant immune reconstitution, preserved T-cell reconstitution, and better clinical outcomes.
In this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 x 10(5)-1 x 10(8) cells/kg/dose) were administered on days -2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database. After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype. Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 (https://clinicaltrials.gov/ct2/show/NCT01904136).

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