High Incidence of Early Human Herpesvirus-6 Infection in Children Undergoing Haploidentical Manipulated Stem Cell Transplantation for Hematologic Malignancies
Por:
Perruccio, K, Sisinni, L, Perez-Martinez, A, Valentin, J, Capolsini, I, Massei, MS, Caniglia, M, Cesaro, S
Publicada:
1 dic 2018
Resumen:
Human herpesvirus-6 (HHV-6) infection is increasingly recognized among allogeneic hematopoietic stem cell transplantation (HSCT) recipients, with 30% at risk of reactivation in the haploidentical setting. It has been associated with encephalitis, acute graft-versus-host disease, and graft failure. Here we report 2 cohorts of pediatric haploidentical manipulated HSCT in which, despite many differences, HHV-6 reactivation and disease occurred with very high incidence compared with data reported in the literature and represented the main early post-transplant infectious complication compared with other viral, bacterial, or fungal infections.
The 2 cohorts were recruited at the pediatric transplant centers of Perugia (n = 13), Barcelona (n = 10), and Madrid (n =15). All patients received myeloablative conditioning regimens and 2 different types of ex vivo graft manipulation: CD34(*). selection and regulatory T cell/conventional T cell infusion in 13 patients and CD45RA T cell depletion in 25 patients. Antiviral prophylaxis was acyclovir in 33 and foscarnet in 5 patients. HHV-6 DNAemia was checked by quantitative or qualitative PCR. In vitro experiments demonstrated that donor CD4(*) T cells are the reservoir of HHV-6 and suggested a role of the graft composition in both transplant settings (rich in CD4(*) T cells) in the high rate of HHV-6 infections.
All patients presented very early HHV-6 DNAemia after transplantation, and although viremic, 9 patients (24%) developed symptomatic limbic encephalitis. All patients responded to antiviral treatment, and none died of infection, although 2 experienced long-term neurologic sequelae (22%). Moreover, 6 patients presented organ involvement in absence of other causes: 1 hepatitis, 1 pneumonia, 2 gastroenteritis, and 2 multiorgan involvement (1 encephalitis, pneumonia, and gastritis; 1 pneumonia and enteritis). Incidences of other viral, bacterial, and fungal diseases were lower in both cohorts. In vitro, HHV-6 was found to infect only CD4(+) fraction of the graft. Co-culturing CD4(+) T cells with CD56(+) natural killer (NK) cells eliminated the virus, demonstrating the main role of NK cells in the antiviral immune response.
All 38 pediatric patients undergoing these manipulated haploidentical HSCTs showed HHV-6 reactivation, and 14 of 38 developed HHV-6 disease with similar features in terms of timing, morbidity, response to treatment, and outcome. The graft composition in both transplant platforms, rich in CD4(+) T cells and poor in Nit cells, seems to play a key role. HHV-6 DNAemia surveillance was useful to diagnose and treat preemptively HHV-6 infection. (C) 2018 American Society for Blood and Marrow Transplantation.
Filiaciones:
Perruccio, K:
Santa Maria Misericordia Hosp, Pediat Oncol Hematol, Perugia, Italy
Sisinni, L:
Santa Creu Hosp, Pediat Hematol, Barcelona, Spain
Perez-Martinez, A:
La Paz Hosp, Pediat Hematol, Madrid, Spain
Valentin, J:
La Paz Hosp, Pediat Hematol, Madrid, Spain
Capolsini, I:
Santa Maria Misericordia Hosp, Pediat Oncol Hematol, Perugia, Italy
Massei, MS:
Santa Maria Misericordia Hosp, Pediat Oncol Hematol, Perugia, Italy
Caniglia, M:
Santa Maria Misericordia Hosp, Pediat Oncol Hematol, Perugia, Italy
Cesaro, S:
Azienda Ospeda Univ lntegrata, Pediat Hematol Oncol, Verona, Italy
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