Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation.
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.
Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|University Paris-Diderot, Paris, France.|Monacord, Centre Scientifique de Monaco, Monaco.|Clinical Hospital, Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Preto, Brazil.
Renato
R
Cunha
Clinical Hospital, Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Preto, Brazil.
Marco A
MA
Zago
Barcelona Cord Blood Bank, Barcelona, Spain.
Sergio
S
Querol
Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|University Paris-Diderot, Paris, France.|Monacord, Centre Scientifique de Monaco, Monaco.
Fernanda
F
Volt
Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|University Paris-Diderot, Paris, France.|Monacord, Centre Scientifique de Monaco, Monaco.|Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.
Annalisa
A
Ruggeri
La Fe University Hospital, Valencia, Spain.
Guillermo
G
Sanz
Besançon Cord Blood Bank, Besançon, France.
Fabienne
F
Pouthier
José Carreras Cord Blood Bank, Düsseldorf, Germany.
Gesine
G
Kogler
Madrid Cord Blood Bank, Madrid, Spain.
José L
JL
Vicario
Pavia Cord Blood Bank, Pavia, Italy.|Service of Immunohematology and Transfusion Medicine, Policlinico San Matteo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy.|Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
Paola
P
Bergamaschi
Firenze Cord Blood Bank, Firenze, Italy.
Riccardo
R
Saccardi
Malaga Cord Blood Bank, Malaga, Spain.
Carmen H
CH
Lamas
Vall d'Hebron Hospital, Barcelona, Spain.
Cristina
C
Díaz-de-Heredia
Timone Children Hospital, Marseille, France.
Gerard
G
Michel
Sainte-Justine University Health Center, Montreal, Canada.
Henrique
H
Bittencourt
Clinical Hospital, Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Preto, Brazil.
Marli
M
Tavella
Clinical Hospital, Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Preto, Brazil.
Rodrigo A
RA
Panepucci
Mathematics Institute, São Paulo University, São Paulo, Brazil.
Francisco
F
Fernandes
Mathematics Institute, São Paulo University, São Paulo, Brazil.
Julia
J
Pavan
Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|University Paris-Diderot, Paris, France.|Monacord, Centre Scientifique de Monaco, Monaco.
Eliane
E
Gluckman
Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|University Paris-Diderot, Paris, France.|Monacord, Centre Scientifique de Monaco, Monaco.|Oxford University, Oxford, United Kingdom; and.|Serviço de Hematologia, Hemoterapia e Terapia Celular, São Paulo University, São Paulo, Brazil.
Vanderson
V
Rocha
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D015870:Gene Expression; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D000070576:NLR Proteins; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D061349:Unrelated Donors
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; D019653:Myeloablative Agonists; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D020033:Protein Isoforms