title: Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation.
abstract: Double umbilical cord blood (DUCB) transplantation is an accepted transplantation strategy for patients without suitable human leukocyte antigen (HLA) matched donors. However, DUCB transplantation is associated with increased morbidity and mortality because of slow recovery of immunity and a high risk of infection. To define the differences in immune reconstitution between DUCB transplantation and HLA matched unrelated donor (MUD) transplantation, we performed a detailed, prospective analysis of immune reconstitution in 42 DUCB recipients and 102 filgrastim-mobilized unrelated peripheral blood stem cell recipients. Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort compared with the MUD cohort for 1 to 6 months posttransplantation (P < .001), including naive (CD45RO-) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25) T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the DUCB cohort and numbers remained significantly greater from 3 to 24 months after transplantation (P = .001). CD56CD16 natural killer (NK) cells also recovered more rapidly in DUCB recipients and remained significantly greater from 1 to 24 months after transplantation. B cell activating factor (BAFF) levels were higher in the DUCB cohort at 1 month (P < .001), were similar in both cohorts at 3 and 6 months, and were lower in the DUCB cohort at 12 months (P = .002). BAFF/CD19 B cell ratios were lower in the DUCB cohort at 3 (P = .045), 6 (P = .02), and 12 months (P = .002) after transplantation. DUCB recipients had more infections within the first 100 days after transplantation (P < .001), and there was less chronic graft-versus-host disease (P < .001), but there were no differences in cumulative incidence of relapse, nonrelapse death, progression-free survival, or overall survival between the 2 groups. These results suggest that increased risk of infections is specifically associated with delayed reconstitution of all major T cell subsets, but the increased risk is limited to the first 3 months after DUCB transplantation. There is no increased risk of relapse, suggesting that graft-versus-leukemia activity is maintained. Early reconstitution of B cells and NK cells may, in part, account for these findings.
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
authors.forename: Caron A
authors.initials: CA
authors.lastname: Jacobson
authors.forename: Amin T
authors.initials: AT
authors.lastname: Turki
authors.forename: Sean M
authors.initials: SM
authors.lastname: McDonough
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Stevenson
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Grace
authors.initials: G
authors.lastname: Kao
authors.forename: Maria I
authors.initials: MI
authors.lastname: Herrera
authors.forename: Carol G
authors.initials: CG
authors.lastname: Reynolds
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Karen
authors.initials: K
authors.lastname: Ballen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D006680:HLA Antigens