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EFFECT OF CYP3A5 GENE POLYMORPHISMS ON TACROLIMUS CONCENTRATION AND ADVERSE EVENTS IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL
Author(s): ,
xin chen
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
rongli zhang
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
weihua zhai
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
qiaoling ma
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
aiming pang
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
donglin yang
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
yi he
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
jialin wei
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
erlie jiang
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
,
sizhou feng
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
mingzhe han
Affiliations:
cell transplant center,Chinese Academy of Medical Sciences Institute of Hematology and Blood Disease,tianjin,China
EHA Library. Chen X. 06/09/21; 324452; PB1781
Xin Chen
Xin Chen
Contributions
Abstract

Abstract: PB1781

Type: Publication Only

Session title: Stem cell transplantation - Clinical

Background
Acute graft-versus-host disease (aGVHD) is one of the major life-threatening complications after HSCT. Prevention of severe aGVHD is crucial to the success of HSCT.

Aims
To investigate the relationship between CYP3A5 gene polymorphisms and tacrolimus concentration and acute graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT).

Methods
Retrospective analysis the clinical data of 35 Chinese adult patients received allo-HSCT from 2019.7 to 2020.2. Bone marrow samples were collected before transplantation for CYP3A5 genotyping. Intravenous infusion of tacrolimus and short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15ng / ml). The incidence of III-IV aGVHD in patients with CYP3A5*1 alleles was higher than that in patients with CYP3A5*3/*3 gene (26.3 + 10.1% vs 6.2 + 6.1%, P=0.115).

Results
In 16 HSCT patients with CYP3A5 * 3 / * 3 gene, the initial concentration of tacrolimus (9.82 vs 8.53 ng / ml), the initial concentration / dose (C / D) ratio (5.72 vs 4.26 ng / ml / mg), and the median C / D ratio in the first two weeks after HSCT (5.29 vs 4.61 ng / ml / Mg, 5.65 vs 4.56 ng / ml / mg) were significantly higher than 19 patients with at least one CYP3A5 * 1 allele (P = 0.026, 0.001, 0.037, 0.045).

Conclusion
CYP3A5 genotype directed administration may help to achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD and improve the efficacy of transplantation.

Keyword(s): Allogeneic hematopoietic stem cell transplant, Gene expression, Graft-versus-host disease (GVHD), Tacrolimus

Abstract: PB1781

Type: Publication Only

Session title: Stem cell transplantation - Clinical

Background
Acute graft-versus-host disease (aGVHD) is one of the major life-threatening complications after HSCT. Prevention of severe aGVHD is crucial to the success of HSCT.

Aims
To investigate the relationship between CYP3A5 gene polymorphisms and tacrolimus concentration and acute graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT).

Methods
Retrospective analysis the clinical data of 35 Chinese adult patients received allo-HSCT from 2019.7 to 2020.2. Bone marrow samples were collected before transplantation for CYP3A5 genotyping. Intravenous infusion of tacrolimus and short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15ng / ml). The incidence of III-IV aGVHD in patients with CYP3A5*1 alleles was higher than that in patients with CYP3A5*3/*3 gene (26.3 + 10.1% vs 6.2 + 6.1%, P=0.115).

Results
In 16 HSCT patients with CYP3A5 * 3 / * 3 gene, the initial concentration of tacrolimus (9.82 vs 8.53 ng / ml), the initial concentration / dose (C / D) ratio (5.72 vs 4.26 ng / ml / mg), and the median C / D ratio in the first two weeks after HSCT (5.29 vs 4.61 ng / ml / Mg, 5.65 vs 4.56 ng / ml / mg) were significantly higher than 19 patients with at least one CYP3A5 * 1 allele (P = 0.026, 0.001, 0.037, 0.045).

Conclusion
CYP3A5 genotype directed administration may help to achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD and improve the efficacy of transplantation.

Keyword(s): Allogeneic hematopoietic stem cell transplant, Gene expression, Graft-versus-host disease (GVHD), Tacrolimus

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