title: Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune Recovery and Outcome.
abstract: Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life-threatening pathogen in allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively evaluated 54 adult patients who developed positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6 reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients, in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients. Twenty-nine patients developed acute graft-versus-host disease (GVHD), mainly grade III-IV, and 15 had concomitant cytomegalovirus reactivation. The median absolute CD3+lymphocyte count was 207 cells/µL. We reported the following clinical manifestations: fever in 43 patients, skin rash in 22, hepatitis in 19, diarrhea in 24, encephalitis in 10, BM suppression in 18, and delayed engraftment in 11. Antiviral pharmacologic treatment was administered to 37 patients; nonetheless, the mortality rate was relatively high in this population (overall survival [OS] at 1 year, 38% ± 7%). A better OS was significantly associated with a CD3+cell count ≥200/µL at the time of HHV-6 reactivation (P = .0002). OS was also positively affected by the absence of acute GVHD grade III-IV (P = .03) and by complete disease remission (P = .03), but was not significantly influenced by steroid administration, time after alloSCT, type of antiviral prophylaxis, plasma viral load, or organ involvement. Although HHV-6 detection typically occurred early after alloSCT, better T cell immune reconstitution seems to have the potential to improve clinical outcomes. Our findings provide new insight into the interplay between HHV-6 and the transplanted immune system.
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Greco
authors.affiliation: University of Milan, Milan, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Crucitti
authors.affiliation: Experimental Hematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Noviello
authors.affiliation: Laboratory of Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Racca
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Mannina
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Forcina
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lorentino
authors.affiliation: Experimental Hematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Valtolina
authors.affiliation: Laboratory of Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Rolla
authors.affiliation: Laboratory of Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Roee
authors.initials: R
authors.lastname: Dvir
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giglio
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Barbanti
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lupo Stanghellini
authors.affiliation: Infectious Disease Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Oltolini
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunogenetics, Leukemia, Genomics, and Immunobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.affiliation: Infectious Disease Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scarpellini
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Carrabba
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Corti
authors.affiliation: Laboratory of Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
authors.affiliation: Experimental Hematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: ciceri.fabio@hsr.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D003587:Cytomegalovirus; D005077:Exanthema Subitum / Q000821:virology; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019349:Roseolovirus Infections / Q000209:etiology*; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D000075442:Transplantation, Haploidentical / Q000009:adverse effects* / Q000401:mortality; D016896:Treatment Outcome; D014775:Virus Activation; D014777:Virus Diseases / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D013256:Steroids
keywords: Allogeneic hematopoietic stem cell transplantation; Human herpesvirus 6; T cell immune reconstitution