title: Risk Factors for and the Clinical Impact of Cytomegalovirus and Epstein-Barr Virus Infections in Pediatric Recipients of TCR-α/β- and CD19-Depleted Grafts.
abstract: Alpha/beta T cell and CD19 depletion are used to improve the outcomes of hematopoietic stem cell transplantation (HSCT). We evaluated the burden of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in pediatric patients after this HSCT type. A cohort of 182 patients with malignant (n = 114) or nonmalignant (n = 68) disorders was transplanted from either matched unrelated (n = 124) or haploidentical (n = 58) donors. The cumulative incidence of CMV and EBV viremia were 51% and 33%, respectively. Acute graft-versus-host disease (GVHD) grades II to IV, D-/R+ serology, and malignant HSCT indications were associated with increased risk of CMV viremia. CMV disease developed in 10 patients (6%). The occurrence of CMV viremia was not associated with inferior outcomes. Acute GVHD grade ≥ II was the only factor significantly associated with an increased risk of EBV viremia. Rituximab significantly decreased the rate of EBV reactivation in a subgroup that received a higher B cell dose in the graft. The rate of EBV-associated disease was .5%, and EBV viremia did not affect survival. TCR-α/β and CD19 depletion are associated with a significant rate of CMV viremia that does not affect survival. The hazard of EBV post-transplant lymphoproliferative disease (PTLD) is eliminated by the combination of CD19 depletion and rituximab.
authors.affiliation: Clinical Immunology Unit, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Laberko
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogoyavlenskaya
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Shelikhova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Shekhovtsova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Balashov
authors.affiliation: Department of Statistics, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Voronin
authors.affiliation: Transfusion Medicine Service, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Kurnikova
authors.affiliation: Transplantation Immunology and Immunotherapy Laboratory, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Boyakova
authors.affiliation: Molecular Biology Laboratory, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Raykina
authors.affiliation: Molecular Biology Laboratory, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Varvara
authors.initials: V
authors.lastname: Brilliantova
authors.affiliation: Infection Control Service, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pirumova
authors.affiliation: Medical Department, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Novichkova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Maschan
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Electronic address: mmaschan@yandex.ru.
authors.forename: Michael
authors.initials: M
authors.lastname: Maschan
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts / Q000276:immunology*; D018941:Antigens, CD19 / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000209:etiology*; D020031:Epstein-Barr Virus Infections / Q000209:etiology*; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000517:prevention & control; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome; D014766:Viremia / Q000209:etiology; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000069283:Rituximab
keywords: Cytomegalovirus; Epstein-Barr virus; Haploidentical; Immune recovery; Matched unrelated; TCR-α/β depletion