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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation

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Cunha, Renato ; Zago, Marco A. ; Querol, Sergio ; Volt, Fernanda ; Ruggeri, Annalisa ; Sanz, Guillermo ; Pouthier, Fabienne ; Kogler, Gesine ; Vicario, Jose L. ; Bergamaschi, Paola ; Saccardi, Riccardo ; Lamas, Carmen H. ; Diaz-de-Heredia, Cristina ; Michel, Gerard ; Bittencourt, Henrique ; Tavella, Marli ; Panepucci, Rodrigo A. ; Fernandes, Francisco ; Pavan, Julia ; Gluckman, Eliane ; Rocha, Vanderson ; Marrow, European Soc Blood ; Paulo, Univ Sao
Total Authors: 23
Document type: Journal article
Source: Blood; v. 129, n. 4, p. 525-532, JAN 26 2017.
Web of Science Citations: 4
Abstract

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, andCTLA4. 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 x 10(7)/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). Weperformed 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. (AU)

FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
Grantee:Berenice Bilharinho de Mendonça
Support Opportunities: Research Projects - Thematic Grants