Goal-Oriented Monitoring of Cyclosporine Is Effective for Graft-versus-Host Disease Prevention after Hematopoietic Stem Cell Transplantation in Sickle Cell Disease and Thalassemia Major

IF 4.3 Q1 Medicine
Alexandra Gauthier , Nathalie Bleyzac , Nathalie Garnier , Kamila Kebaili , Philippe Joly , Marie-Pierre Goutagny , Isabelle Mollet , Sylvain Goutelle , Cécile Renard , Yves Bertrand
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引用次数: 3

Abstract

Graft-versus-host disease (GVHD) is an important challenge and a major cause of morbidity and mortality in children after hematopoietic stem cell transplant (HSCT). Herein we report our institution's experience of goal-oriented Bayesian monitoring for cyclosporine (CsA) used alone as GVHD prophylaxis during the post-transplant period in pediatric patients with thalassemia major (TM) or sickle cell anemia (SCA) undergoing HLA-matched HSCT. We also studied evolution of chimerism. Twenty-six consecutive patients (SCA, 14; TM, 12) underwent matched sibling donor (MSD) HSCT from 2004 to 2014. All patients received a myeloablative conditioning regimen. GVHD prophylaxis consisted of 20 mg/kg antithymocyte globulin in the conditioning regimens and then CsA alone in the post-transplant period. Target CsA trough blood concentration (TBC) was 150 ± 20 ng/mL. At last follow-up, all patients were alive and free of disease, even in cases of mixed chimerism. Engraftment occurred in all patients. No patient developed grades II to IV acute GVHD, 4 patients developed acute grade I skin GVHD, and only 1 presented with chronic pulmonary GVHD. A better control of GVHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role. Further investigations are required, but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible with that obtained with MSDs.

定向监测环孢素对镰状细胞病和重度地中海贫血患者造血干细胞移植后移植物抗宿主病预防有效
移植物抗宿主病(GVHD)是儿童造血干细胞移植(HSCT)后发病和死亡的一个重要挑战和主要原因。在此,我们报告了本机构在接受hla匹配的HSCT的患有地中海贫血(TM)或镰状细胞贫血(SCA)的儿童患者移植后单独使用环孢素(CsA)作为GVHD预防的目标导向贝叶斯监测的经验。我们也研究了嵌合的进化。26例连续患者(SCA, 14例;2004年至2014年,12例患者接受了兄弟姐妹匹配供体(MSD) HSCT。所有患者均接受清髓调理方案。GVHD预防包括在调节方案中使用20 mg/kg抗胸腺细胞球蛋白,然后在移植后单独使用CsA。靶CsA血药浓度(TBC)为150±20 ng/mL。在最后的随访中,即使是混合嵌合的病例,所有患者都存活且无疾病。所有患者均有移植。没有患者发展为II至IV级急性GVHD, 4例患者发展为急性I级皮肤GVHD,仅有1例患者表现为慢性肺GVHD。本文所述的通过严格监测CsA TBC来更好地控制GVHD和免疫抑制是有希望的,并且可能发挥关键作用。需要进一步的研究,但这项研究为提高TM和SCA中替代供体的HSCT的存活率和安全性提供了新的视角,使其达到与MSDs相容的水平。
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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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