Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation

Blood. 2005 Mar 15;105(6):2608-13. doi: 10.1182/blood-2004-04-1667. Epub 2004 Nov 16.

Abstract

Thymic function is critical for immune reconstitution after hematopoietic stem cell transplantation (HSCT). We evaluated recipient thymic function before HSCT by quantifying T-cell receptor excision circles (TRECs) in pretransplantation peripheral blood lymphocytes from 102 patients who received HSCs from an HLA-identical sibling for malignant (n = 87) or nonmalignant diseases (n = 15). Median TREC value before transplantation was 257 TRECs per 150,000 CD3+ cells (range, 0-42,746). We assessed 172 TRECs per 150,000 CD3+ cells as the most discriminating TREC value for survival in a first cohort of patients (n = 62). This cut-off was validated in a second independent prospective group of 40 patients. In the 102 patients, a TREC value greater than or equal to 172 was associated with a better survival (P < .000 01), a decreased incidence of grade II-IV acute graft-versus-host disease (GVHD; P = .017), chronic GVHD (P = .023), and bacterial (P = .003) and cytomegalovirus (CMV) infection (P = .024). In a multivariate analysis, low pretransplantation TREC values were associated with a higher incidence of CMV infection (hazard ratio [HR] = 2.0, P = .06) and severe bacterial infections (HR = 2.8, P = .036). Finally, high TREC values (HR = 6.6, P = .002) and ABO compatibility (HR = 2.7, P = .02) were associated with a better survival. Therefore, recipient host thymic function assessment could be helpful in predicting HSCT outcome and identifying patients who require a close immunologic monitoring.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System
  • Adolescent
  • Adult
  • CD3 Complex / blood*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / mortality
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / mortality*
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Histocompatibility
  • Histocompatibility Testing
  • Humans
  • Lymphocytes*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Antigen, T-Cell / analysis
  • Receptors, Antigen, T-Cell / blood*
  • Siblings*
  • Transplantation, Homologous

Substances

  • ABO Blood-Group System
  • CD3 Complex
  • Receptors, Antigen, T-Cell