title: Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation.
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.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité Assistance Publique-Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM) U396, Hôpital Saint-Louis, Paris, CEDEX 10, France. clave@histo.chu-stlouis.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
authors.forename: Kimmo
authors.initials: K
authors.lastname: Talvensaari
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Corinne
authors.initials: C
authors.lastname: Douay
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Appert
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.forename: Federico
authors.initials: F
authors.lastname: Garnier
authors.forename: Alain
authors.initials: A
authors.lastname: Filion
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000017:ABO Blood-Group System; D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000097:blood / Q000209:etiology / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000097:blood*; D035781:Siblings; D014184:Transplantation, Homologous
chemical_list: D000017:ABO Blood-Group System; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell