The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus‐6B encephalitis after naïve T‐cell‐depleted allogeneic stem cell transplantation

• Published in: Transfusion (Philadelphia, Pa.) Pa.), 2021-05, Vol.61 (5), p.1505-1517
• Main Authors: Gasior, Mercedes, Ferreras, Cristina, Paz, Raquel, Bueno, David, Mozo, Yasmina, Sisinni, Luisa, Canizales, Juan Torres, González, Berta, Olivas‐Mazón, Raquel, Marcos, Antonio, Romero, Ana Belén, Constanzo, Aída, Mirones, Isabel, Fernández‐Arroyo, Alba, Balas, Antonio, Vicario, Jose Luis, Escudero, Adela, Yuste, Víctor Jiménez, Pérez‐Martínez, Antonio
• Format: Article
• Language: English
• Subjects: Antigens; CD34 antigen; CD4 antigen; CD45RA antigen; Depletion; Encephalitis; Epstein-Barr virus; Graft-versus-host reaction; Grafting; haploidentical stem cell transplantation; Hematopoietic stem cells; Histocompatibility antigen HLA; human herpesvirus‐6; Immune reconstitution; Immunological memory; Leukocytes; Lymphocytes; Lymphocytes T; Memory cells; Natural killer cells; Patients; Stem cell transplantation; Stem cells; Survival; Transplantation
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.16354

Background Naïve T‐cell‐depleted grafts have been employed as an ex vivo T‐cell depletion (TCD) platform to prevent graft‐versus‐host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T‐cell reconstitution after allogenic hematopoietic stem cell transplantation (allo‐HSCT). CD45RA− memory T cells confer protection against viruses such as cytomegalovirus, Epstein–Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)‐6B encephalitis among pediatric allo‐HSCT patients. Methods We report the first 18 consecutive allo‐HSCT, 16 haplo‐HSCT, and two human leukocyte antigen‐matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV‐6B encephalitis. Results Engraftment was achieved in 94.5% of cases; 2‐year overall survival, event‐free survival, and GvHD/relapse‐free survival were 87.2% (95% CI 78.6–95.8), 67.3% (95% CI 53.1–81.5), and 64% (95% CI 50.5–78.1), respectively. HHV‐6B reactivation occurred in 7 of the haplo‐HSCT patients, six of who received a cell infusion with an NK/CD4 ratio