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.
Subject(s)
Encephalitis/prevention & control , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human/isolation & purification , Killer Cells, Natural/transplantation , Lymphocyte Depletion , Roseolovirus Infections/prevention & control , Adolescent , Adoptive Transfer/methods , Child , Child, Preschool , Encephalitis/immunology , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Herpesvirus 6, Human/immunology , Humans , Infant , Killer Cells, Natural/immunology , Male , Roseolovirus Infections/immunology , T-Lymphocytes/immunology , Transplantation, Homologous/methodsABSTRACT
Ruxolitinib, a selective Janus Kinase (JAK) 1/2 inhibitor, is a promising treatment for the steroid-refractory graft-vs-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT). Most studies have been performed in the adult population showing efficacy against GvHD. In this retrospective study, we evaluated the outcomes of 19 children who received ruxolitinib for refractory acute or chronic GvHD (cGvHD) after HSCT from two Pediatric Hemato-Oncology Departments in Spain between March 2017 and December 2018. Patients received a median number of 4 (IQR 2) previous lines of treatment before starting ruxolitinib. The overall response rate in acute GvHD (aGvHD) and cGvHD was 87% and 91%, respectively. Complete response (CR) was observed in 37% of aGvHD and 8.3% of cGvHD. Remarkably, 43% and 40% of patients with steroid-refractory gastrointestinal aGvHD and lung cGvHD achieved CR. During ruxolitinib treatment, there were 36%, 31%, and 10% infections caused by viruses, bacteria, and fungi, respectively. Overall, four patients interrupted ruxolitinib due to infectious complications, hematological, and liver toxicity. The 2-year overall survival was 71.9% (CI 95% 58.6-85.2). Our experience supports the use of ruxolitinib as an effective treatment for steroid-refractory acute and cGvHD in children with a moderate toxicity profile.
