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 language | English |
|---|---|
| Pages (from-to) | 525-532 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 129 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 26 2017 |
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ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology
Cite this
Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation. / Cunha, Renato; Zago, Marco A.; Querol, Sergio; Volt, Fernanda; Ruggeri, Annalisa; Sanz, Guillermo; Pouthier, Fabienne; Kogler, Gesine; Vicario, José L.; Bergamaschi, Paola; Saccardi, Riccardo; Lamas, Carmen H.; Díaz-De-Heredia, Cristina; Michel, Gerard; Bittencourt, Henrique; Tavella, Marli; Panepucci, Rodrigo A.; Fernandes, Francisco; Pavan, Julia; Gluckman, Eliane; Rocha, Vanderson; Cord Blood Committee Cellular Therapy-Immunobiology Working Party of the European Society for Blood and Marrow Transplantation.
In: Blood, Vol. 129, No. 4, 26.01.2017, p. 525-532.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation
AU - Cunha, Renato
AU - Zago, Marco A.
AU - Querol, Sergio
AU - Volt, Fernanda
AU - Ruggeri, Annalisa
AU - Sanz, Guillermo
AU - Pouthier, Fabienne
AU - Kogler, Gesine
AU - Vicario, José L.
AU - Bergamaschi, Paola
AU - Saccardi, Riccardo
AU - Lamas, Carmen H.
AU - Díaz-De-Heredia, Cristina
AU - Michel, Gerard
AU - Bittencourt, Henrique
AU - Tavella, Marli
AU - Panepucci, Rodrigo A.
AU - Fernandes, Francisco
AU - Pavan, Julia
AU - Gluckman, Eliane
AU - Rocha, Vanderson
AU - Cord Blood Committee Cellular Therapy-Immunobiology Working Party of the European Society for Blood and Marrow Transplantation
PY - 2017/1/26
Y1 - 2017/1/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014894859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014894859&partnerID=8YFLogxK
U2 - 10.1182/blood-2016-06-722249
DO - 10.1182/blood-2016-06-722249
M3 - Article
VL - 129
SP - 525
EP - 532
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -