Volumen: 20 # Number : 1
Publication Date : Enero - Abril Year: 2016
Transforming Growth Factor-B1 Functional polymorphisms
in myeloablative sibling hematopoietic
stem cell transplantation.
Authors: Berro M, Palau V, Rivas M, Foncuberta C, Vitriu A,
Remaggi G, Martínez Rolon J, Jaimovich G, Requejo A,
Feldman L, Larripa, Padros K, Rodriguez MB, Kusminsky G
Abstract: Allogeneic hematopoietic stem cell transplantation
(HSCT) using sibling donors is a life- saving intervention
for patients with hematological malignancies.
Numerous genetic factors in both patient and
donor play a role in the outcome of the procedure.
Several functional polymorphisms have been identified
in TGF-B1 gene, such as a single nucleotide
polymorphism (SNP) at codon 10 of exon 1. We
have previously published significant impact of this
SNP on unrelated donor (UD) transplant outcome.
We hypothesized that TGF-B1 SNP may influence
the outcome of sibling donor HSCT similarly to
UD. Two hundred and forty five patient/donor pairs
who underwent a sibling donor HSCT in our centers
were genotyped for the presence of a SNP at codon
10 and
25 by an allele-specific PCR. Transplants took place
between January 2000 and December 2014 and the
median follow up time was 4.4 years. Codon 10
SNP did not impact clinical outcomes in the whole
cohort. When we analyzed the myeloablative cohort,
significant differences were found. Patients 10
CC had more aGvHD III-IV compared to TT/TC
(22% vs 7.2%, p=0.01). Additionally 10 CC donors
were associated with an increase in severe chronic
GvHD (32% vs 16%, MA HR 9.0, 95% CI 1.3 62.5, p=0.02). Regarding survival outcomes, codon
10 CC patients had a significant increase in 1 year
treatment related mortality (29% vs. 7%, MA HR
7.1, 95% CI 1.3-37.1, p=0.02) and NRM (1-5 years
CC 28-32% vs. TC/TT 7-10%, Gray’s test p<0.01;
HR 5.1, 95% CI 1.36-19.2, p=0.01). Codon 10 TT
donor’s receptors experienced a significant increase
in relapse rate (1-5 years TT 37-51% vs. TC 19-25%
vs. CC 13-19%, Gray’s test p=0.02, HR 2.4, 95% CI
1.2-4.9, p=0.01) a trend to a lower DFS (1-5 years
57-36% vs 73-63%, log rank p=0.05, HR 2.5, 95%
CI 0.97-6.5 p=0.05) and a significant decrease in
OS compared to other genotypes (1-5 years TT 69-
50% vs. TC/CC 77-69%, log-rank p=0.04, HR 1.9,
95% CI 0.99-3.8, p=0.05). We confirm our previous
findings in UD, that patient codon 10 CC results in
an increase in NRM. In addition we found that in
sibling donor-myeloablative HSCT codon 10 TT
donors might be associated with an increase in relapse
rate with a consequent decrease in DFS and
OS. These results should be confirmed in larger series.
Identification of these SNPs pre-transplant will
allow for transplant conditioning and immunosuppression
regimens to be tailored to the individual
patient, as well as assisting in the most appropriate
choice of donor.
Key words: Hematopoyetic stem cell trasplantation,
TGFB1,
Polymorphisms,
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