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

Biol Blood Marrow Transplant. 2017 Mar;23(3):483-490. doi: 10.1016/j.bbmt.2016.12.635. Epub 2016 Dec 27.

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.

Keywords: Cytomegalovirus; Epstein-Barr virus; Haploidentical; Immune recovery; Matched unrelated; TCR-α/β depletion.

MeSH terms

  • Adolescent
  • Adult
  • Allografts / immunology*
  • Antigens, CD19 / analysis*
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / etiology*
  • Epstein-Barr Virus Infections / etiology*
  • Female
  • Graft vs Host Disease / complications
  • Graft vs Host Disease / virology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Infant
  • Lymphoproliferative Disorders / prevention & control
  • Male
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Retrospective Studies
  • Risk Factors
  • Rituximab / therapeutic use
  • Treatment Outcome
  • Viremia / etiology
  • Young Adult

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Rituximab