Sixty-one percent of individuals had either a response less than CR or prolonged/progressive disease at the time of transplant

Sixty-one percent of individuals had either a response less than CR or prolonged/progressive disease at the time of transplant. We found that CIK cell infusion was safe and feasible to infuse in the ambulatory setting as early consolidation therapy, with related rates of 100-day time and 1-yr grade II-IV aGVHD. cells were infused in 31 of 44 individuals treated on study and contained mainly CD3+CD8+NKG2D+ cells along with significantly expanded CD3+CD56+ cells. Results were compared to a retrospective historic cohort of 100 individuals. We found that this one-time CIK infusion did not increase the rate of FDC by Day time +90. On an intention-to-treat analysis, 2-yr non-relapse mortality (6.8%, 95%CI: 0C14.5%), event-free UCPH 101 survival (27.3%, 95%CI: 16.8C44.2%), and overall survival (50.6%, 95%CI: 37.5C68.2%) were related to our historical cohort. Cumulative incidence of grade II-IV acute graft versus UCPH 101 sponsor disease at 1-yr was 25.1% (95%CI: 12C38.2%). On univariate analysis, the presence of monosomal or complex karyotype was adversely associated with relapse-free and overall survival. Given the favorable security profile of CIK cell infusion, strategies such as repeat dosing or genetic modification are well worth exploration. This trial was authorized at Clinicaltrials.gov (). from peripheral blood tradition with interferon (IFN)-, interleukin (IL)-2, and anti-CD3.6,7 CIK cells harvested with this approach generally include populations of CD3+CD56+ as well as CD3+CD314/NKG2D+ (natural killer group 2, member D) cells.7,8 CD3+CD56+ cells have been shown to have non-MHC restricted anti-tumor cytotoxic activity.9 NKG2D, a UCPH 101 member of the C-type lectin-like receptor family,10 has been associated with anti-tumor immune activity.11 CIK cells have been shown to have anti-tumor effects in severe combined immunodeficiency murine models with tumor, and in clinical studies.7,12 While the majority of CIK cell clinical studies have been in the autologous setting in hematologic neoplasms and stable tumors, a few studies possess evaluated allogeneic donor-derived CIK cell infusion for hematological neoplasms relapsed after allo-HCT.8,13C15 In the first reported phase I allogeneic UCPH 101 CIK cell infusion study,13 11 individuals with hematologic disease relapse after allo-HCT received repeated infusions of CIK cells having a median of 12.4 X 106/kg total CIK cells per patient; in this study, 2 individuals with combined donor chimerism (MDC) consequently converted to FDC, including 1 patient with CMML and 1 patient with MDS, both of whom experienced a complete response.13 In our earlier phase I/II study of allogeneic CIK cells from matched related sibling donors in 18 individuals with hematologic malignancies relapsed after allo-HCT, we evaluated dose escalations from 1 X 107/kg (n=4), 5 X 107/kg (n=6), to the highest planned dose of 1 1 X 108/kg CD3+ cells (n=8). We found that the CIK cells could be safely given in the relapsed establishing and had a low incidence of acute graft versus sponsor disease (aGVHD).8 We hypothesized that early post-transplant consolidation with donor-derived CIK cells would be well-tolerated, have anti-tumor activity, and promote early donor chimerism, without significantly affecting rates of aGVHD. As post-transplant consolidation with allogeneic CIK cells has not been previously analyzed, we chose a dose of a one-time infusion of 1 1 X 108/kg CD3+ donor-derived CIK cells to be given between days +21C35 following TLI-ATG centered allo-HCT for individuals with MDS, MPN, t-MN and secondary acute myeloid leukemia (s-AML). Our main objective was to determine the proportion of individuals achieving FDC by Day time +90 post-transplant. Our secondary objectives were to determine 2-yr OS, 2-yr event-free survival (EFS), aGVHD incidence, and to assess NKG2D ligand manifestation. Materials and Methods Study individuals and donors This was a single center, nonrandomized, open-label phase II trial (study protocol 217) evaluating the effects of a one-time infusion of donor-derived CIK cells following allo-HCT with TLI-ATG conditioning for individuals with myeloid neoplasms. This study was authorized by the Scientific Review Committee and Institutional Review Table of Stanford University or college, and the FDA (IND quantity 14307). It was performed in accordance with the principles of the Declaration of Helsinki. All subjects provided written educated consent and were treated at Stanford University or college Medical Center. Fifty-six individuals provided educated consent; 12 individuals were found to be ineligible and 44 individuals were treated on study between 03/2011 through 02/2016. Data were censored using last follow-up check out before 08/2017 to allow minimal follow-up of 18 months. Study eligibility Eligibility criteria are further detailed in supplementary methods. Briefly, recipient qualified diagnoses included MDS; MPN excluding Keratin 7 antibody Philadelphia positive chronic myeloid leukemia (CML); MDS-MPN overlap syndromes; s-AML; and t-MN (including t-MDS, t-MPN, t-MDS-MPN overlap and t-AML). To be eligible, recipients had to be greater than 50 years of age or felt to be at UCPH 101 high risk for toxicity from myeloablative conditioning, with availability of a fully HLA-matched or solitary antigen/allele mismatched related or unrelated donor. Recipient exclusion criteria included: uncontrolled central nervous system involvement; Karnofsky performance score.