Patients with acute myeloid leukemia (AML) in children and young adults (YA) who recur following allogeneic hematopoietic cell transplantation (HCT) had a very poor prognosis. Donor lymphocyte infusions (DLIs) and standard salvage chemotherapy had minimal curative promise. Previous research showed that natural killer (NK) cells might be activated ex vivo with IL-12, -15, and -18 to produce memory-like (ML) NK cells with improved anti-leukemia responses. 

In a phase 1 experiment, researchers used donor ML NK cells to treat 9 pediatric/YA patients with post-HCT relapsed AML. Fludarabine, cytarabine, and filgrastim were given to the patients, followed by an infusion of donor lymphocytes and ML NK cells from the initial HCT donor 2 weeks later. ML NK cells were successfully produced from haploidentical, related, and unrelated donors. Donor-derived ML NK cells grew and maintained an ML multidimensional mass cytometry phenotype for more than 3 months after infusion.

Furthermore, ML NK cells demonstrated long-term functional responses, as shown by leukemia-induced interferon production. On day 28, four of the 8 evaluable patients had achieved full remission following DLI and ML NK cell adoptive transfer. 2 patients were in remission for more than 3 months, and 1 patient was in remission for more than 2 years. There was no severe toxicity. The work showed that in the absence of exogenous cytokines, donor ML NK cells grew and persisted with powerful antileukemic activity in a suitable post-HCT immunological milieu. ML NK cells combined with DLI represented a potential immunotherapy platform for AML that had relapsed following allogeneic HCT.

Reference:ashpublications.org/blood/article-abstract/139/11/1670/482906/Donor-memory-like-NK-cells-persist-and-induce?redirectedFrom=fulltext