Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis
Open Access
- 20 May 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 115 (20), 4111-4119
- https://doi.org/10.1182/blood-2009-09-244145
Abstract
Umbilical cord blood grafts are increasingly used as sources of hematopoietic stem cells in adults. Data regarding the outcome of this approach in adults are consistent with delayed and insufficient immune reconstitution resulting in high infection-related morbidity and mortality. Using cytomegalovirus (CMV)–specific immunity as a paradigm, we evaluated the status, mechanism, and clinical implications of immune reconstitution in adults with hematologic malignancies undergoing unrelated double unit cord blood transplantation. Our data indicate that CD8+ T cells capable of secreting interferon-γ (IFN-γ) in a CMV-specific enzyme-linked immunosorbent spot (ELISpot) assay are detectable at 8 weeks after transplantation, before reconstitution of thymopoiesis, but fail to clear CMV viremia. Clearance of CMV viremia occurs later and depends on the recovery of CD4+CD45RA+ T cells, reconstitution of thymopoiesis, and attainment of T-cell receptor rearrangement excision circle (TREC) levels of 2000 or more copies/μg DNA. In addition, overall survival was significantly higher in patients who displayed thymic regeneration and attainment of TREC levels of 2000 or more copies/μg DNA (P = .005). These results indicate that reconstitution of thymopoiesis is critical for long-term clinical outcome in adult recipients of umbilical cord blood transplant. The trial was prospectively registered at http://www.clinicaltrials.gov (NCT00133367).Keywords
This publication has 54 references indexed in Scilit:
- Thymic involution and immune reconstitutionTrends in Immunology, 2009
- Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitutionClinical Immunology, 2008
- CD134-Allodepletion Allows Selective Elimination of Alloreactive Human T Cells without Loss of Virus-Specific and Leukemia-Specific EffectorsTransplantation and Cellular Therapy, 2008
- Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewingBlood, 2007
- Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic diseaseBlood, 2007
- Double Unrelated Reduced-Intensity Umbilical Cord Blood Transplantation in AdultsTransplantation and Cellular Therapy, 2007
- Antigen-Specific T-Lymphocyte Function After Cord Blood TransplantationTransplantation and Cellular Therapy, 2006
- Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantationBlood, 2006
- Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignanciesBone Marrow Transplantation, 2006
- Cytomegalovirus Immune Reconstitution Occurs in Recipients of Allogeneic Hematopoietic Cell Transplants Irrespective of Detectable Cytomegalovirus InfectionTransplantation and Cellular Therapy, 2005