Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation.
Fiche publication
Date publication
janvier 2017
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr POUTHIER Fabienne
Tous les auteurs :
Cunha R, Zago MA, Querol S, Volt F, Ruggeri A, Sanz G, Pouthier F, Kogler G, Vicario JL, Bergamaschi P, Saccardi R, Lamas CH, Díaz-de-Heredia C, Michel G, Bittencourt H, Tavella M, Panepucci RA, Fernandes F, Pavan J, Gluckman E, Rocha V,
Lien Pubmed
Résumé
We evaluated the impact of recipient and cord blood unit (CBU) genetic polymorphisms related to immune response on outcomes after unrelated cord blood transplantations (CBTs). Pretransplant DNA samples from 696 CBUs with malignant diseases were genotyped for NLRP1, NLRP2, NLRP3, TIRAP/Mal, IL10, REL, TNFRSF1B, and CTLA4. HLA compatibility was 6 of 6 in 10%, 5 of 6 in 39%, and ≥4 of 6 in 51% of transplants. Myeloablative conditioning was used in 80%, and in vivo T-cell depletion in 81%, of cases. The median number of total nucleated cells infused was 3.4 × 10/kg. In multivariable analysis, patients receiving CBUs with GG-CTLA4 genotype had poorer neutrophil recovery (hazard ratio [HR], 1.33; P = .02), increased nonrelapse mortality (NRM) (HR, 1.50; P < .01), and inferior disease-free survival (HR, 1.41; P = .02). We performed the same analysis in a more homogeneous subset of cohort 1 (cohort 2, n = 305) of patients who received transplants for acute leukemia, all given a myeloablative conditioning regimen, and with available allele HLA typing (HLA-A, -B, -C, and -DRB1). In this more homogeneous but smaller cohort, we were able to demonstrate that GG-CTLA4-CBU was associated with increased NRM (HR, 1.85; P = .01). Use of GG-CTLA4-CBU was associated with higher mortality after CBT, which may be a useful criterion for CBU selection, when multiple CBUs are available.
Mots clés
Adaptor Proteins, Signal Transducing, genetics, Adolescent, Adult, Alleles, Apoptosis Regulatory Proteins, genetics, CTLA-4 Antigen, genetics, Child, Child, Preschool, Cord Blood Stem Cell Transplantation, Disease-Free Survival, Female, Fetal Blood, cytology, Gene Expression, Genotype, HLA Antigens, genetics, Hematologic Neoplasms, genetics, Histocompatibility Testing, Humans, Infant, Male, Middle Aged, Myeloablative Agonists, therapeutic use, Polymorphism, Genetic, Proportional Hazards Models, Protein Isoforms, genetics, Retrospective Studies, Transplantation Conditioning, Unrelated Donors
Référence
Blood. 2017 01 26;129(4):525-532