Donor-Derived Cytokine-Induced Killer Cell Infusion as Consolidation after Nonmyeloablative Allogeneic Transplantation for Myeloid Neoplasms

Rupa Narayan, Jonathan E. Benjamin, Omid Shah, Lu Tian, Keri Tate, Randall Armstrong, Bryan J. Xie, Robert Lowsky, G. Laport, Robert S. Negrin, Everett H. Meyer

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Non-myeloablative conditioning, such as with total lymphoid irradiation and antithymocyte globulin (TLI-ATG), has allowed allogeneic hematopoietic cell transplantation (allo-HCT) with curative potential for older patients and those with comorbid medical conditions with myeloid neoplasms. However, early achievement of full donor chimerism (FDC) and relapse remain challenging. Cytokine-induced killer (CIK) cells have been shown to have antitumor cytotoxicity. Infusion of donor-derived CIK cells has been studied for hematologic malignancies relapsed after allo-HCT but has not been evaluated as post-transplant consolidation. In this phase II study, we prospectively studied whether a one-time infusion of 1 × 108/kg CD3+ donor-derived CIK cells administered between day +21 and day +35 after TLI-ATG conditioning could improve achievement of FDC by day +90 and 2-year clinical outcomes in patients with myeloid neoplasms. CIK cells, containing predominantly CD3+CD8+NKG2D+ cells along with significantly expanded CD3+CD56+ cells, were infused in 31 of 44 patients. Study outcomes were compared to outcomes of a retrospective historical cohort of 100 patients. We found that this one-time CIK infusion did not increase the rate of FDC by day +90. On an intention-to-treat analysis, 2-year non-relapse mortality (6.8%; 95% confidence interval [CI], 0-14.5%), event-free survival (27.3%; 95% CI, 16.8-44.2%), and overall survival (50.6%; 95% CI, 37.5-68.2%) were similar to the values seen in the historical cohort. The cumulative incidence of grade II-IV acute graft-versus-host disease at 1-year was 25.1% (95% CI, 12-38.2%). On univariate analysis, the presence of monosomal or complex karyotype was adversely associated with relapse-free survival and overall survival. Given the favorable safety profile of CIK cell infusion, strategies such as repeat dosing or genetic modification merit exploration. This trial was registered at ClinicalTrials.gov (NCT01392989).

Original languageEnglish (US)
Pages (from-to)1293-1303
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number7
DOIs
StatePublished - Jul 2019
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Cell therapy
  • Cytokine-induced killer cells
  • Myelodysplastic syndrome
  • Non-myeloablative conditioning transplantation
  • Reduced-intensity conditioning transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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