脾大可能增加地中海贫血低风险匹配相关供体移植的排斥风险,这种风险可以通过调节期间额外的免疫抑制部分克服

IF 4.3 Q1 Medicine
Stalin Ramprakash , C.P. Raghuram , Priya Marwah , Rajpreet Soni , Deepa Trivedi , Sadaf Khalid , Naila Yaqub , Fatima Itrat , Sarah Khan Gilani , Tatheer Zahra , Rakesh Dhanya , Rajat Kumar Agarwal , Lawrence Faulkner
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引用次数: 2

摘要

严重地中海贫血综合征(ST)可通过骨髓移植(BMT)高度治愈,但仍可能发生排斥反应。我们回顾性分析了完全匹配的相关供体移植,以确定孤立性脾肿大是否是排斥反应的独立危险因素,以及是否可以通过修改条件方案来降低这种风险。在这项研究中,我们比较了189例连续低风险ST移植患者的脾肿大和非脾肿大患者在2个顺序调节方案中的排异率:方案A(2013年8月至2016年12月):busulfan(口服14mg /kg,未调整到血清水平)、环磷酰胺(200mg /kg)和抗胸腺细胞球蛋白(ATG) (Genzyme (Sanofi, Paris, France) 4mg /kg或Fresenius (Grafalon, Neovii Biotech GmbH, Gräfelfing德国)16mg /kg,第12天至第10天),方案B。2017年1月至2018年9月,在脾大和/或性别不匹配移植的情况下,前期增加氟达拉滨总剂量150 mg, ATG剂量增加至7 mg/kg,与方案A相同。与方案A相比,方案B的总排斥率(RRs)(16%对6.5%,P = 0.023)和治疗相关死亡率(TRM)(9.9%对2.8%,P = 0.038)均显著改善。Cox回归分析显示,两种治疗方案在脾肿大患者中的RR改善尤为显著(RR分别为54.5%和6.5%,P = 0.00015;TRM为18.2%对6.5%,P = 0.25)(风险比4.13;置信区间为1.61 ~ 10.6;p = .003)。通过在标准ATG-Busulfan- Cyclophosphamide (ATG-Bu-Cy)方案中加入氟达拉滨,可以克服脾大相关排斥反应风险的增加,而不会显著增加移植相关的发病率和死亡率,也不会在bmt前进行脾切除术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Splenomegaly May Increase the Risk of Rejection in Low-Risk Matched Related Donor Transplant for Thalassemia, This Risk Can Be Partially Overcome by Additional Immunosuppression during Conditioning

Severe thalassemia syndromes (ST) are highly curable by bone marrow transplant (BMT), but rejection may still occur. We retrospectively analyzed our fully matched related donor transplants to establish if isolated splenomegaly is an independent risk factor for rejection and if this risk can be reduced by modifying the conditioning protocol. In this study, we compared rejection rates between patients with and without splenomegaly in 189 consecutive low-risk ST transplants across 2 sequential conditioning regimens: regimen A (August 2013 to December 2016): busulfan (14 mg/kg oral, not adjusted to serum levels), cyclophosphamide (200 mg/kg), and anti-thymocyte globulin (ATG) (Genzyme (Sanofi, Paris, France) 4 mg/kg or Fresenius (Grafalon, Neovii Biotech GmbH, Gräfelfing Germany) 16 mg/kg on days –12 to –10), and regimen B: same backbone as regimen A except fludarabine total dose of 150 mg was added upfront and ATG dose was increased to 7 mg/kg in case of splenomegaly and/or sex-mismatched transplants (January 2017 to September 2018). Compared with regimen A, in regimen B, both overall rejection rates (RRs) (16% versus 6.5%, P = .023) and treatment-related mortality (TRM) (9.9% versus 2.8%, P = .038) improved significantly. By Cox regression analysis, the improvement in RR between the 2 protocols was particularly significant in patients with splenomegaly (RR 54.5% versus 6.5%, P = .00015; TRM 18.2% versus 6.5%, P = .25) (hazard ratio, 4.13; confidence interval, 1.61 to 10.6; P = .003). The increased risk of rejection related to splenomegaly can be overcome by adding fludarabine to the standard ATG-Busulfan- Cyclophosphamide (ATG-Bu-Cy) protocol without significantly increasing transplant-related morbidity and mortality or resorting to splenectomy pre-BMT.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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