title: General and Virus-Specific Immune Cell Reconstitution after Double Cord Blood Transplantation.
abstract: Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared with HLA-matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an antithymocyte globulin-containing regimen at our institution. A subset of 65 patients was prospectively evaluated for recovery of T, natural killer (NK), and B cells, and in 46 patients we also examined viral-specific T cell recovery against adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus, and influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of nonrelapse mortality and overall survival. Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rima M
authors.initials: RM
authors.lastname: Saliba
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
authors.forename: Ann
authors.initials: A
authors.lastname: Leen
authors.affiliation: Department of Laboratory Medicine, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jorgensen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Amanda
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Julianne
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Charles
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Amir
authors.initials: A
authors.lastname: Hamdi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rohtesh S
authors.initials: RS
authors.lastname: Mehta
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Roy F
authors.initials: RF
authors.lastname: Chemaly
authors.affiliation: Hematology/Oncology and Bone Marrow Transplant, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California.
authors.forename: Ila M
authors.initials: IM
authors.lastname: Saunders
authors.affiliation: Division of Blood and Marrow Transplantation, Children's National Hospital System and George Washington University, Washington, DC.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas. Electronic address: norma.dominguez@mdanderson.org.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D012306:Risk; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014777:Virus Diseases / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000821:virology
chemical_list: D000956:Antigens, Viral; D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists
keywords: Absolute lymphocyte count; B cells; NK cells; Post-transplant; Post-transplant infections; T cells