A prospective study of allogeneic transplantation from unrelated donors for chronic granulomatous disease with target busulfan-based reduced-intensity conditioning.
A prospective study of allogeneic transplantation from unrelated donors for chronic granulomatous disease with target busulfan-based reduced-intensity conditioning.
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一项针对慢性肉芽肿性疾病的异体移植的前瞻性研究，采用基于白消安的目标降低强度调理。
DOI：
10.1038/s41409-018-0271-9
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kato M
中科院分区：
文献类型：
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作者：
Osumi T;Tomizawa D;Kawai T;Sako M;Inoue E;Takimoto T;Tamura E;Uchiyama T;Imadome K;Taniguchi M;Shirai R;Yoshida M;Ando R;Tsumura Y;Fuji H;Matsumoto K;Shioda Y;Kiyotani C;Terashima K;Onodera M;Matsumoto K;Kato M
致编者：慢性肉芽肿病（CGD）是一种由吞噬细胞nadph氧化酶功能损伤引起的原发性免疫疾病。尽管治疗有所改善，但CGD病例仍与严重感染、手术发作和住院有关。几十年来，CGD患者的生存率有所提高，但在保守治疗时，感染仍然是发病率和死亡率的主要原因。同种异体造血干细胞移植（HSCT）是治疗CGD[3]的一种方法。最近的一项调查显示，在未移植的成年病例中，医疗和社会障碍的发生率很高，这表明对于CGD病例，HSCT的适应症可以延长[10]。历史上使用过清髓调节方案，并且与未使用HSCT的病例相比，已获得更高的生存率。在这十年中，减少强度调节（RIC）方案已被越来越多地采用，以避免移植相关的发病率和死亡率。然而，先前RIC方案的挑战导致移植物衰竭或混合嵌合的高风险，这可能与移植物丢失和其他并发症相关[6,7]。最近，欧洲骨髓移植（EBMT）小组进行的一项多中心前瞻性临床试验表明，针对来自hla匹配供体（包括HLA-9/10匹配供体）的HSCT，基于靶向丁硫丹（BU）的调节方案实现了高无事件生存率（89%），具有出色的供体嵌合性和最小的毒性bb0。然而，需要进一步的证据来建立针对CGD的HSCT的最佳调理方案。我们进行了一项前瞻性临床试验，旨在确认RIC与靶向BU在非相关供者（包括hla错配供者）的HSCT中的有效性和安全性。在我们的研究中，调理包括靶向BU，氟达拉滨（FLU）和抗胸腺球蛋白（ATG）。部是
To the Editor: Chronic granulomatous disease (CGD) is a primary immunodisorder caused by impairment of the phagocyte NADPH-oxidase function. Despite improvements in treatment, cases of CGD have been associated with serious infection, episodes of surgery, and hospitalization [1]. Survival probability of CGD patients has improved over the decades, but infections are still a major cause of morbidity and mortality when treated conservatively [2]. Allogeneic hematopoietic stem cell transplantation (HSCT) is performed as a curative approach for CGD [3]. A recent survey revealed high rates of medical and social handicaps in non-transplanted cases reaching adulthood that suggest an extended indication of HSCT for CGD cases [4]. Myeloablative conditioning regimens have been used historically, and have achieved improved survival compared to cases without HSCT [5]. In this decade, reduced-intensity conditioning (RIC) regimens have been increasingly adopted to avoid transplantation-related morbidity and mortality. However, previous challenges of RIC regimens resulted in high risk of graft failure or mixed chimerism that could be associated with graft loss and other complications [6, 7]. Recently, a multicenter prospective clinical trial conducted by the European Bone Marrow Transplantation (EBMT) Group demonstrated that a targeted busulfan (BU)-based conditioning regimen for HSCT from HLA-matched donors (including HLA-9/10 matched donors) achieved a high rate (89%) of event-free survival with excellent donor chimerism and minimal toxicity [8]. However, further evidence is required to establish an optimal conditioning regimen in HSCT for CGD. We conducted a prospective clinical trial, aiming to confirm the efficacy and safety of RIC with targeted BU in HSCT from unrelated donors, including HLA-mismatched donors. In our study, conditioning consisted of targeted BU, fludarabine (FLU), and anti-thymoglobulin (ATG). BU was