Mass Cytometry and Functional Analysis of NK cells on CTN-1101 Trial to Determine the Impact of Graft Source on Immune Reconstitution With Focus on Relapse Protection and Overall Survival — ASN Events

Mass Cytometry and Functional Analysis of NK cells on CTN-1101 Trial to Determine the Impact of Graft Source on Immune Reconstitution With Focus on Relapse Protection and Overall Survival (#140)

Peter Hinderlie 1 , Claudio Brunstein 2 , David Kazadi 1 , Zachary B Davis 1 , Ephraim J Fuchs 3 , Amanda Russell 1 , Marissa Kaufman 1 , Paul V O’Donnell 4 , Daniel Weisdorf 1 , Jeffrey S Miller 1 , Martin Felices 1
  1. University of Minnesota, Minneapolis, MINNESOTA, United States
  2. Cleveland Clinic, Cleveland, OH, USA
  3. Johns Hopkins University, Baltimore, MD, USA
  4. Harvard Medical School, Boston, MA, USA

Acute myeloid leukemia (AML) is one of the most common subtypes of leukemia in adults and hematopoietic stem cell transplantation (HSCT) is used as a common and effective treatment for this disease.  Though this therapeutic approach has been employed for decades, it is not well understood how the source of the graft affects immune reconstitution, particularly NK cell reconstitution, and what the corresponding effect this reconstitution is on relapse protection and overall survival.  We compared the phenotypes of different immune subsets at 28- and 60-days post-transplant from AML recipients that received either haploidentical (Haplo) or umbilical cord blood (UCB) transplants obtained in the CTN-1101 randomized trial (N=64 per cohort).  Using two distinct CyTOF panels, each consisting of 42 analytes, we observed that graft source significantly impacts immune reconstitution and the phenotypic characteristics of those immune cell populations.  In addition to these CyTOF panels, we have evaluated NK cell function in response to exposure to K562 cells and cytokine stimulation (IL-12/18). Our functional data indicates that UCB transplant results in higher functional capacity NK cells, particularly earlier in a post-transplant setting.  To analyze the CyTOF data obtained in this study we employed the Astrolabe platform in an unsupervised fashion to determine biologic and expression differences between graft sources.  Early post-transplant we noted increased expression of transcription factors PLZF , Fas, 4-1BB and Eomesoderim, as well as surface receptors Fas and 41BB on UCB transplant NK cells versus Haplo transplant NK cells  Finally, we also used this platform to determine immune drivers, linked or unlinked to graft source, for disease-free survival, overall survival, performance score and protection against GVHD.