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异基因干细胞移植前氟达拉滨和苏消安预处理的毒理学效应

Toxicological effects of fludarabine and treosulfan conditioning before allogeneic stem-cell transplantation.

作者信息

Remberger Mats, Törlen Johan, Serafi Ibrahim El, Garming-Legert Karin, Björklund Andreas, Ljungman Per, Sundin Mikael, Hassan Moustapha, Mattsson Jonas

机构信息

Center for Allogeneic Stem Cell Transplantation Unit, Karolinska University Hospital, SE-141 86, Stockholm, Sweden.

Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Int J Hematol. 2017 Oct;106(4):471-475. doi: 10.1007/s12185-017-2320-3. Epub 2017 Aug 28.

Abstract

We studied early potential treosulfan-related toxicity in 118 patients treated with treosulfan-based conditioning before allogeneic hematopoietic stem-cell transplantation. Most patients (n = 93) had a hematological malignancy. In 80 cases, a HLA-A, -B and -DR matched unrelated donor was used, while 33 patients had a HLA-identical sibling donor, and five received an HLA-A, -B or -DR allele mismatched, unrelated donor. Levels of AST, ALT, and bilirubin were significantly increased 1 week after HSCT compared to before HSCT. However, only a few patients had transaminase levels >2 to 3 × the upper normal level. All patients became neutropenic; 61% were already so at the time of graft infusion. Nearly all patients engrafted, except for three who died very early. Non-relapse mortality was 7.5% at 100 days and 11.9% at 1 year after HSCT. Veno-occlusive disease of the liver occurred in one patient and hemorrhagic cystitis in two patients. This study shows that early regimen-related toxicity after HSCT was low despite similar marrow toxicities compared to myeloablative regimens.

摘要

我们研究了118例在异基因造血干细胞移植前接受基于苏消安预处理的患者中与苏消安相关的早期潜在毒性。大多数患者(n = 93)患有血液系统恶性肿瘤。80例患者使用了HLA-A、-B和-DR配型相合的无关供者,33例患者有HLA相同的同胞供者,5例接受了HLA-A、-B或-DR等位基因不相合的无关供者。与造血干细胞移植前相比,造血干细胞移植后1周时AST、ALT和胆红素水平显著升高。然而,只有少数患者转氨酶水平>正常上限的2至3倍。所有患者均出现中性粒细胞减少;61%在输注移植物时就已出现。除3例早期死亡患者外,几乎所有患者均实现造血重建。造血干细胞移植后100天时非复发死亡率为7.5%,1年时为11.9%。1例患者发生肝静脉闭塞病,2例患者发生出血性膀胱炎。本研究表明,尽管与清髓性方案相比骨髓毒性相似,但造血干细胞移植后早期方案相关毒性较低。

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