title: Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients.
abstract: BACKGROUND
  Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality.
  
  
  METHODS
  A detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning. Recovery of thymopoiesis was assessed using analysis of signal joint T-cell receptor rearrangement excision circles. The impact of recovery of thymopoiesis at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those time points was evaluated by univariate and multivariate Cox regression analyses.
  
  
  RESULTS
  The cumulative incidence of severe infections at 12 months after transplantation was 66% with a median number of 1.64 severe infectious episodes per patient. Patients in whom thymopoiesis did not recover were at significantly higher risk of severe infections according to multivariable analysis. Hazard ratios indicated 3- and 9-fold increases in severe infections at 6 and 12 months, respectively. Impaired recovery of thymopoiesis also translated into a higher risk of non-relapse mortality and outweighed pre-transplant risk factors including age, donor type, and disease risk-status.
  
  
  CONCLUSIONS
  These results indicate that patients who fail to recover thymopoiesis after allogeneic hematopoietic stem cell transplantation are at very high risk of severe infections and adverse clinical outcome.
authors.affiliation: Erasmus MC/Daniel den Hoed Cancer Center, Department of Hematology, EA Rotterdam, The Netherlands.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Wils
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Annoek E C
authors.initials: AE
authors.lastname: Broers
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Posthumus-van Sluijs
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Gratama
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology / Q000276:immunology* / Q000401:mortality*; D020127:Recovery of Function / Q000276:immunology*; D012307:Risk Factors; D015996:Survival Rate; D013950:Thymus Gland / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous