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 glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. 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. The GSTA1*A/*A genotype 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 of GST and CYP polymorphisms 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 a GSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.

中文翻译：

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剂量调整的环丁砜-环磷酰胺调节接受者中谷胱甘肽S-转移酶和细胞色素P450基因多态性的分析。

尽管在实时BU剂量调整后达到了推荐的白消安（BU）浓度，但静脉闭塞性疾病（VOD）的零星发病率仍继续发生。为了探讨谷胱甘肽S-转移酶（GST）和细胞色素P450（CYP）基因型对血浆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。包括55名患者（中位年龄38岁；范围21-67）。其中49例接受了剂量调整的BU / CY治疗。26名患者接受了与人类白细胞抗原相同的兄弟姐妹的移植，其中26名来自无关的供体。GSTA1 * A / * A基因型与曲线下的BU首剂量较低区域（AUC1st）显着相关。我们发现，AUC1st较高的患者在移植后的第一个月内血清总胆红素显着较高，但这未必与随后的VOD发生有关。我们进一步分析了GST和CYP多态性与VOD发生的可能联系，发现所研究的多态性均与VOD发生率无关。关于移植的结果，在多变量分析中，GSTM1阳性患者表现出较低的复发率和较好的总体生存率。这些结果表明接受BU / CY调理的患者中GSTM1阳性基因型可防止异基因造血干细胞移植后血液系统恶性肿瘤复发。我们进一步分析了GST和CYP多态性与VOD发生的可能联系，发现所研究的多态性均与VOD发生率无关。关于移植的结果，在多变量分析中，GSTM1阳性患者表现出较低的复发率和较好的总体生存率。这些结果表明接受BU / CY调理的患者中GSTM1阳性基因型可防止异基因造血干细胞移植后血液系统恶性肿瘤复发。我们进一步分析了GST和CYP多态性与VOD发生的可能联系，发现所研究的多态性均与VOD发生率无关。关于移植的结果，在多变量分析中，GSTM1阳性患者表现出较低的复发率和较好的总体生存率。这些结果表明接受BU / CY调理的患者中GSTM1阳性基因型可防止异基因造血干细胞移植后血液系统恶性肿瘤复发。