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在接受allo-SCT 的髓系恶性肿瘤患者中,降低强度预处理方案中兔抗胸腺细胞球蛋白剂量从 2.5mg/kg 增加到 5mg/kg,可降低急性和慢性移植物抗宿主病。

The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT.

机构信息

Department of Hematology, Transplantation Program, Gene and Cell Therapy program, Institut Paoli Calmettes, Marseille, France.

出版信息

Bone Marrow Transplant. 2012 May;47(5):639-45. doi: 10.1038/bmt.2012.3. Epub 2012 Feb 6.

Abstract

We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r-ATG2; n=22). Grade 2-4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P<0.001). The relapse incidences (RI) at 24 months were 18.9% and 28.5% in r-ATG1 and r-ATG2 groups, respectively (P=0.640). Overall and PFS were not different between the r-ATG1 and r-ATG2 groups. r-ATG dose at 5 mg/kg in the setting of RIC seems a good balance allowing GVHD prevention and antitumor effect with a remarkable reduction of GVHD incidence without an identical level of increased relapse rate.

摘要

我们之前报道过,氟达拉滨、BU 和 2.5mg/kg 的兔抗胸腺细胞球蛋白(r-ATG)的低强度预处理(RIC)方案有效,但与急性和慢性移植物抗宿主病(GVHD)的高发生率相关。因此,我们将 r-ATG 的剂量增加到 5mg/kg。在本报告中,我们分析了 2000 年至 2010 年间 87 例接受 HLA 同基因兄弟姐妹供体异基因造血干细胞移植(allo-SCT)的 AML 或骨髓增生异常综合征(MDS)患者。RIC 方案由氟达拉滨、BU 和 r-ATG 组成,1 天内给予 2.5mg/kg(r-ATG1;n=53)或 2 天内每天给予 2.5mg/kg(r-ATG2;n=22)。r-ATG1 和 r-ATG2 组第 100 天 2-4 级急性 GVHD 的发生率分别为 30.2%和 8.8%(P=0.038)。广泛慢性 GVHD 的发生率分别为 60.4%和 12%(P<0.001)。r-ATG1 和 r-ATG2 组 24 个月的复发率分别为 18.9%和 28.5%(P=0.640)。r-ATG1 和 r-ATG2 组的总生存(OS)和无进展生存(PFS)无差异。RIC 方案中 r-ATG 剂量为 5mg/kg 似乎是一种较好的平衡方案,既能预防 GVHD,又能发挥抗肿瘤作用,显著降低 GVHD 发生率,而不会增加相同水平的复发率。

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