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

Stefan O. Ciurea, Piyanuch Kongtim, Doris Soebbing, Prashant Trikha, Gregory Behbehani, Gabriela Rondon, Amanda Olson, Qaiser Bashir, Alison M. Gulbis, Kaur Indreshpal, Katayoun Rezvani, Elizabeth J. Shpall, Roland Bassett, Kai Cao, Andrew St Martin, Steven Devine, Mary Horowitz, Marcelo Pasquini, Dean A. Lee, Richard E. Champlin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 × 105–1 × 108 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).

Original languageEnglish (US)
Pages (from-to)155-164
Number of pages10
JournalLeukemia
Volume36
Issue number1
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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