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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

2021; Wiley; Volume: 61; Issue: 5 Linguagem: Inglês

10.1111/trf.16354

1537-2995

Mercedes Gasior Kabat, Cristina Ferreras, Raquel de Paz, David Bueno, Yasmina Mozo, Luisa Sisinni, Juan Manuel Torres, Berta González, Raquel Olivas‐Mazón, Antônio Marcos, Ana Belén Romero, Aída Constanzo, Isabel Mirones, Alba Fernández‐Arroyo, A. Balas, José L. Vicário, Adela Escudero, Víctor Jiménez‐Yuste, Antonio Pérez‐Martínez,

Hematopoietic Stem Cell Transplantation

Abstract 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 <2. None of the patients developed encephalitis. Conclusions In this clinical study, we show that early adoptive NK cell infusion after a 45RA + TCD allo‐HSCT graft is safe and can prevent HHV‐6B encephalitis. We recommend infusing adoptive NK cells after allo‐HSCT using CD45RA + TCD grafts.