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

Renato Cunha, Marco A. Zago, Sergio Querol, Fernanda Volt, Annalisa Ruggeri, Guillermo Sanz, Fabienne Pouthier, Gesine Kogler, José L. Vicario, Paola Bergamaschi, Riccardo Saccardi, Carmen H. Lamas, Cristina Díaz-De-Heredia, Gerard Michel, Henrique Bittencourt, Marli Tavella, Rodrigo A. Panepucci, Francisco Fernandes, Julia Pavan, Eliane GluckmanVanderson Rocha, Cord Blood Committee Cellular Therapy-Immunobiology Working Party of the European Society for Blood and Marrow Transplantation

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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, 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 × 107/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.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
JournalBlood
Volume129
Issue number4
DOIs
Publication statusPublished - Jan 26 2017

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Cunha, R., Zago, M. A., Querol, S., Volt, F., Ruggeri, A., Sanz, G., Pouthier, F., Kogler, G., Vicario, J. L., Bergamaschi, P., Saccardi, R., Lamas, C. H., Díaz-De-Heredia, C., Michel, G., Bittencourt, H., Tavella, M., Panepucci, R. A., Fernandes, F., Pavan, J., ... Cord Blood Committee Cellular Therapy-Immunobiology Working Party of the European Society for Blood and Marrow Transplantation (2017). Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation. Blood, 129(4), 525-532. https://doi.org/10.1182/blood-2016-06-722249