scholarly journals Significance of CTLA-4 and CD14 genetic polymorphisms in clinical outcome after allogeneic stem cell transplantation

2007 ◽  
Vol 40 (10) ◽  
pp. 1001-1002 ◽  
Author(s):  
A M Vannucchi ◽  
S Guidi ◽  
P Guglielmelli ◽  
S Glinz ◽  
L Lombardini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Genetic Polymorphisms ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation

No Direct Effect of NOD2/CARD15 Variants On Clinical Outcome After Non-Myeloablative Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4322-4322
Author(s):  
Hanneke M. van der Straaten ◽  
Martine M. Paquay ◽  
Marcel G.J. Tilanus ◽  
Leo F. Verdonck ◽  
Cynthia Huisman
Keyword(s):  
Stem Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Significant Prognostic Factor ◽  
Wild Type

Abstract Abstract 4322 Background Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic haematopoietic stem cell transplantation. The effect of the NOD2/CARD15 polymorphism seems to be associated with donor source as well as type of conditioning regimen. Methods We reviewed NOD2/CARD15 mutations in all donor/recipient pairs of 192 consecutive patients who received non-myeloablative allogeneic stem cell transplantation(SCT) at our institution between 2002 and 2006. All patients were treated uniformly with fludarabine 30 mg/m2/day for 3 days followed by 200 cGy TBI (n=154) or TBI alone (n=38) and received grafts from HLA-matched related (n=132) or unrelated (n=60) donors. Results Mutated alleles were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. These SNPs, however, did not have a significant impact on clinical outcome data (P > 0.05, Kaplan Meier and Fine & Gray's test). Acute graft-versus-host disease (GVHD) occurred in 24 of 61 (39%) patients with the polymorphism and in 66 of 131 (50%) patients without the polymorphism. Chronic GVHD developed in 28 of 55 (51%) patients with SNP pairs and in 79 of 121 (65%) patients with the wild type. The incidence of transplant-related mortality was 21% in both groups, 13 of 61 patients in the group with the polymorphism and 27 of 131 without the polymorphism. Relapse was seen in 23 of 61 (38%) patients with the SNP pairs and in 48 of 131 (37%) wild type patients. Finally, overall survival was 43% (26/61) in patients with the polymorphism and 39% (51/131) in patients without the polymorphism. Conclusion These data indicate that mutations in the NOD2/CARD15 genes do not influence the clinical outcome of non-myeloablative allogeneic SCT directly. Since NOD2/CARD15 variants are not recognized as a single significant prognostic factor, screening for NOD2/CARD15 when selecting a donor does not seem to have additional value in patients undergoing non-myeloablative SCT. Disclosures: No relevant conflicts of interest to declare.

Cord blood graft composition impacts the clinical outcome of allogeneic stem cell transplantation

2014 ◽  
Vol 16 (2) ◽  
pp. 203-212 ◽  
Author(s):  
H. Wikell ◽  
S. Ponandai-Srinivasan ◽  
J. Mattsson ◽  
J. Gertow ◽  
M. Uhlin
Keyword(s):  
Stem Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Graft Composition

Polymorphisms of NOD2/CARD15 Are Associated with Clinical Outcome in T-Cell Depleted HLA-Identical Sibling Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1408-1408
Author(s):  
Miquel Granell ◽  
Alvaro Urbano-Ispizua ◽  
Juan Ignacio Arostegui ◽  
Francesc Fernandez-Aviles ◽  
Carmen Martinez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
T Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Event Free Survival ◽  
Free Survival

Abstract Three single nucleotide polymorphisms (SNP) in NOD2/CARD15 have been associated with the incidence and severity of acute GVHD following allogeneic stem cell transplantation (allo-SCT). The potential clinical influence of SNP in NOD2/CARD15 in a model of allo-SCT with a low incidence of GVHD, such as T-cell depleted transplants (TCD), has not been studied. We analyzed the association of SNP in NOD2/CARD15 with the outcome of 84 patients undergoing allo-SCT with TCD by means of CD34+ selection. Results were compared with a concurrent group of 94 patients receiving an allo-SCT with unmanipulated grafts (Non-TCD). Transplants were performed in a single institution, donors were HLA identical siblings and all patients received myeloablative-conditioning regimen. Median follow-up was of 30.6 months (range, 0.2–112). SNP 8, 12 and 13 were analyzed by RT-PCR allelic discrimination method in all patients and in 137 donors. SNP in NOD2/CARD15 were detected in 13.8% of patients and in 10.7% of donors. Results of the association of patient’s NOD2/CARD15 genotype and outcome are given in the table. In TCD transplants, independent risk factors associated with event free survival in a multivariate analysis were: patient’s NOD2/CARD15 genotype (RR 2.7, p=0.02), patient’s age (RR 2.3, p=0.03) and conditioning with radiotherapy (RR 2.7, p=0.03). The only association of donor’s NOD2/CARD15 genotype with clinical outcome in the multivariate analysis was with acute GVHD (RR 3.3, p=0.03). In conclusion, polymorphisms in NOD2/CARD15 have a strong association with clinical outcome in TCD transplants, which is independent of GVHD. Overall group (n=178) SNP vs. WT P* TCD (n=84) SNP vs. WT P* Non-TCD (n=94) SNP vs. WT P* WT, wild type; N.S, non significant; * Log-rank test Acute GVHD II–IV 27 vs. 22 N.S 22 vs. 40 N.S 33 vs. 12 N.S Chronic GVHD 61 vs. 35 0.1 29 vs. 14 N.S 100 vs. 44 0.005 Event free survival 21 vs. 47 0.03 17 vs. 48 0.04 22 vs. 31 N.S Overall survival 30 vs. 59 0.01 33 vs. 56 0.04 30 vs. 48 N.S

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