Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing.
Advances in immune assessment, including the development of T-cell receptor excision circle (TREC) assays of thymopoiesis, cytokine-flow cytometry assays of T-cell function, and higher-order phenotyping of T-cell maturation subsets have improved our understanding of T-cell homeostasis. Limited data exist using these methods to characterize immune recovery in adult cord blood (CB) transplant recipients, in whom infection is a leading cause of mortality. We now report the results of a single-center prospective study of T-cell immune recovery after cord blood transplantation (CBT) in a predominantly adult population. Our primary findings include the following: (1) Prolonged T lymphopenia and compensatory expansion of B and natural killer (NK) cells was evident; (2) CB transplant recipients had impaired functional recovery, although we did observe posttransplantation de novo T-cell responses to cytomegalovirus (CMV) in a subset of patients; (3) Thymopoietic failure characterized post-CBT immune reconstitution, in marked contrast to results in other transplant recipients; and (4) Thymopoietic failure was associated with late memory T-cell skewing. Our data suggest that efforts to improve outcomes in adult CB transplant recipients should be aimed at optimizing T-cell immune recovery. Strategies that improve the engraftment of lymphoid precursors, protect the thymus during pretransplant conditioning, and/or augment the recovery of thymopoiesis may improve outcomes after CBT.
Department of Stem Cell Transplantation and Cellular Therapy, M D Anderson Cancer Center, Houston, TX 77030, USA. kkomanduri@mdanderson.org
Krishna V
KV
Komanduri
Lisa S
LS
St John
Marcos
M
de Lima
John
J
McMannis
Steven
S
Rosinski
Ian
I
McNiece
Susan G
SG
Bryan
Indreshpal
I
Kaur
Sean
S
Martin
Eric D
ED
Wieder
Laura
L
Worth
Laurence J N
LJ
Cooper
Demetrios
D
Petropoulos
Jeffrey J
JJ
Molldrem
Richard E
RE
Champlin
Elizabeth J
EJ
Shpall
D036101:Cord Blood Stem Cell Transplantation; D006410:Hematopoiesis; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000502:physiology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008214:Lymphocytes; D011446:Prospective Studies; D012038:Regeneration; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology