Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning
Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning
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白消安-环磷酰胺剂量调整受体谷胱甘肽S-转移酶和细胞色素P450基因多态性分析
DOI：
10.1007/s12185-019-02741-8
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发表时间：
2020
期刊：
影响因子：
2.1
通讯作者：
Murata M
中科院分区：
文献类型：
--
作者：
Terakura S;Onizuka M;Fukumoto M;Kuwatsuka Y;Kohno A;Ozawa Y;Miyamura K;Inagaki Y;Sawa M;Atsuta Y;Suzuki R;Naoe T;Morishita Y;Murata M
尽管在实时调整静脉阻塞(BU)剂量后达到了推荐的白花丹(BU)浓度，但散发性静脉闭塞病(VOD)仍在继续发生。为了探讨谷胱甘肽转移酶(GST)和细胞色素P450(CYP)基因对血浆BU浓度、随后的VOD和移植结果的潜在影响，我们评估了多个GST和CYP基因的多态性。纳入55名患者(中位年龄38岁；范围21-67岁)。其中，49人接受了剂量调整的BU/CY治疗。26名患者接受了人类白细胞抗原相合同胞的移植，26名患者来自无血缘关系的捐赠者。GSTA1*A/*A基因型与较低的BU首剂量曲线下面积(AUC1)显著相关。我们发现，AUC1值较高的患者在移植后第一个月内血清总胆红素显著升高，但这与随后的VOD发展并不一定相关。我们进一步分析了GST和CDP基因多态与VOD发病的可能关联，发现所调查的多态与VOD的发病率均无关联。在移植结果方面，多因素分析显示，GSTM1阳性患者的复发率较低，总体存活率较好。这些结果表明，在接受BU/CY预适应的患者中，aGSTM1阳性基因对异基因造血干细胞移植后血液系统恶性肿瘤的复发具有保护作用。
Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathioneS-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multipleGSTandCYPgenes. Fifty-five patients were included (median age 38 years; range 21–67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical siblings, 26 from unrelated donors. TheGSTA1*A/*Agenotype was significantly associated with lower BU first-dose area under curve (AUC1st). We found that patients with higher AUC1st showed a significantly higher serum total bilirubin during the first month after transplantation, but this was not necessarily associated with subsequent development of VOD. We further analyzed a possible association ofGSTandCYPpolymorphisms and VOD development, and found none of the polymorphisms investigated was associated with VOD incidence. Regarding transplant outcomes,GSTM1-positive patients showed lower relapse rates and better overall survival in multivariate analyses. These results suggest that aGSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.
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影响因子：
1.7
作者：
H. Tsuruta;M. Fukumoto;L. Bax;A. Kohno;Y. Morishita
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DOI：
--
发表时间：
2006
期刊：
Bone Marrow Transplant 37・4
影响因子：
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作者：
Matsui H.;et al.;Narimatsu H et al.;Yanada M et al.;Suzuki M et al.;Inamoto Y et al.;Adachi T et al.;Terakura S et al.
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Terakura S et al.
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Iga, TatsuJi