Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Komanduri KV,St John LS,de Lima M,McMannis J,Rosinski S,McNiece I,Bryan SG,Kaur I,Martin S,Wieder ED,Worth L,Cooper LJ,Petropoulos D,Molldrem JJ,Champlin RE,Shpall EJ

doi

10.1182/blood-2007-05-092130

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

4543-51

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2007-05-092130

journal_volume

110

pub_type

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