TY - JOUR
T1 - Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing
AU - Komanduri, Krishna V.
AU - St. John, Lisa S.
AU - De Lima, Marcos
AU - McMannis, John
AU - Rosinski, Steven
AU - McNiece, Ian
AU - Bryan, Susan G.
AU - Kaur, Indreshpal
AU - Martin, Sean
AU - Wieder, Eric D.
AU - Worth, Laura
AU - Cooper, Laurence J.N.
AU - Petropoulos, Demetrios
AU - Molldrem, Jeffrey J.
AU - Champlin, Richard E.
AU - Shpall, Elizabeth J.
PY - 2007/12/15
Y1 - 2007/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34948863068&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948863068&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-05-092130
DO - 10.1182/blood-2007-05-092130
M3 - Article
C2 - 17671230
AN - SCOPUS:34948863068
SN - 0006-4971
VL - 110
SP - 4543
EP - 4551
JO - Blood
JF - Blood
IS - 13
ER -