Get Outta Here! Addition of Mobilizing Agents to Conditioning Regimen Improves Donor Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation for Wiskott-Aldrich Syndrome.
Get Outta Here! Addition of Mobilizing Agents to Conditioning Regimen Improves Donor Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation for Wiskott-Aldrich Syndrome.
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DOI：
10.1016/j.bbmt.2018.05.003
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Rettig,MichaelP
中科院分区：
文献类型：
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作者：
Rettig,MichaelP
1978年，Parkman et al. [1]首次成功治疗2例Wiskott-Aldrich综合征（WAS）患儿，采用全身照射、甲基苄肼和抗胸腺细胞球蛋白进行清髓性预处理后，移植HLA匹配的骨髓移植物。他们假设需要“免疫抑制和受体造血干细胞的充分减少”来为供体干细胞植入提供“空间”。40年后，Balashov et al. [2]，在这一期的《血液和骨髓移植生物学》中，继续扩展开放骨髓龛或“制造空间”的概念。他们证明，当毒性降低的清髓性预处理方案补充有2种通常用于动员造血干细胞和祖细胞（HSPC）的药物时，WAS患者的异基因供体干细胞移植增强：粒细胞集落刺激因子（G-CSF）和CXCR 4拮抗剂plerixafor [2]。WAS是一种罕见的遗传性X连锁原发性免疫缺陷疾病，由WAS基因功能丧失突变引起[3]。WAS蛋白是所有造血谱系中肌动蛋白细胞骨架的关键调节因子，其缺乏会导致特征性微血小板减少症以及淋巴和骨髓细胞功能障碍[4]。临床评分系统用于对疾病严重程度进行分层。评分为3 - 5分的患者表现出WAS表型，其特征为出血倾向、持续性湿疹、对严重机会性细菌和病毒感染的易感性、自身免疫和炎症并发症以及淋巴恶性肿瘤风险升高[5]。在没有明确治疗的情况下，WAS患者无法存活超过他们生命的第二或第三个十年。
In 1978, Parkman et al.[1] were the first to successfully treat 2 children with Wiskott-Aldrich syndrome (WAS) by transplanting HLA-matched bone marrow grafts after myeloablative conditioning with total body irradiation, procarbazine, and antithymocyte globulin. They hypothesized that “immunosuppression and an adequate reduction in recipient hematopoietic stem cells” were required to provide “space” for donor stem cell engraftment. Forty years later, Balashov et al.[2], in this issue of the Biology of Blood and Marrow Transplantation, continue to expand on the concept of opening marrow niches or “making space.” They demonstrated enhanced allogeneic donor stem cell engraftment in WAS patients when a reduced toxicity myeloablative conditioning regimen was supplemented with 2 agents commonly used to mobilize hematopoietic stem and progenitor cells (HSPCs): granulocyte colony-stimulating factor (G-CSF) and the CXCR4 antagonist plerixafor [2].WAS is a rare inherited X-linked primary immunodeficiency disorder caused by loss-of-function mutations in the WAS gene [3]. The WAS protein is a key regulator of the actin cytoskeleton in all hematopoietic lineages and its deficiency causes characteristic microthrombocytopenia and lymphoid and myeloid cell dysfunction [4]. A clinical scoring system is used to stratify disease severity. Patients with a score from 3 to 5 display a WAS phenotype characterized by a tendency to bleed, persistent eczema, susceptibility to severe opportunistic bacterial and viral infections, autoimmune and inflammatory complications, and an elevated risk of lymphoid malignancies [5]. In the absence of definitive treatment, WAS patients do not survive beyond their second or third decade of life.
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