ABSTRACT
Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56bright /CD16bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106 -107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.
Subject(s)
CD56 Antigen/analysis , Immunotherapy, Adoptive/methods , Killer Cells, Natural/transplantation , Leukemia, Myeloid, Acute/therapy , Receptors, IgG/analysis , Adolescent , Adult , Brazil/epidemiology , CD56 Antigen/immunology , Child , Female , GPI-Linked Proteins/analysis , GPI-Linked Proteins/immunology , Graft vs Host Disease/etiology , Humans , Immunotherapy, Adoptive/adverse effects , Killer Cells, Natural/immunology , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/immunology , Male , Middle Aged , Proof of Concept Study , Receptors, IgG/immunology , Young AdultABSTRACT
Multiple models of donor killer immunoglobulin receptor (KIR) alloreactivity or KIR genotype have been reported to be protective against leukemia relapse after allogeneic transplantation. However, few studies have addressed this topic in the pediatric population. Here, we assessed the outcomes of allogeneic transplantation in children with acute lymphoblastic leukemia (ALL; n = 372) or acute myeloid leukemia (AML; n = 344) who received unrelated donor (URD) transplantation and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005 to 2016. As expected in this pediatric population, most patients underwent myeloablative conditioning while in remission and with bone marrow as a stem cell source. We tested KIR ligand mismatch, KIR gene content (centromeric [Cen] B), KIR2DS1 mismatching, and Cen B/telomeric A using Cox regression models and found that none were significantly associated with either relapse or disease-free survival when considering the entire cohort of patients (ALL and AML), AML, or ALL separately. Moreover, there was no significant association with outcomes in the in vivo T-cell-depleted (ie, serotherapy) cohort. This study, which is the largest analysis of donor KIR in the pediatric acute leukemia population, does not support the use of KIR in the selection of URDs for children undergoing T-replete transplantation.