Robust CD4(+) T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin Journal Article

Authors: Politikos, I.; Lavery, J. A.; Hilden, P.; Cho, C.; Borrill, T.; Maloy, M. A.; Giralt, S. A.; van den Brink, M. R. M.; Perales, M. A.; Barker, J. N.
Article Title: Robust CD4(+) T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin
Abstract: Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA1 T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk. © 2020 by The American Society of Hematology.
Keywords: adult; controlled study; aged; human cell; major clinical study; myeloproliferative disorder; cd8+ t lymphocyte; cohort analysis; b lymphocyte; acute graft versus host disease; acute leukemia; cord blood stem cell transplantation; hematologic malignancy; myelodysplastic syndrome; cd4+ t lymphocyte; therapy delay; lymphoma; natural killer cell; effector cell; cd4 lymphocyte count; memory cell; risk reduction; cyclosporine; cytomegalovirus; graft recipient; ablation therapy; cd45ra antigen; thymocyte antibody; immune reconstitution; immunoprophylaxis; phytohemagglutinin; mycophenolate mofetil; myeloablation; human; male; female; priority journal; article; mortality risk
Journal Title: Blood Advances
Volume: 4
Issue: 1
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2020-01-14
Start Page: 191
End Page: 202
Language: English
DOI: 10.1182/bloodadvances.2019000836
PUBMED: 31935291
PROVIDER: scopus
PMCID: PMC6960461
Notes: Article -- Source: Scopus
Citation Impact
MSK Authors
  1. Sergio Andres Giralt
    824 Giralt
  2. Miguel-Angel Perales
    657 Perales
  3. Juliet N Barker
    312 Barker
  4. Molly Anna Maloy
    259 Maloy
  5. Christina Cho
    107 Cho
  6. Patrick Dale Hilden
    107 Hilden
  7. Taylor Wray Borrill
    20 Borrill
  8. Jessica Ann Lavery
    48 Lavery