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[从健康供体采集造血祖细胞]

[Collection of hematopoietic progenitor cells from healthy donors].

作者信息

Bojanić Ines, Cepulić Branka Golubić, Mazić Sanja

机构信息

Zavod za klinicku transfuziologiju, Klinicki zavod za laboratorijsku dijagnostiku, Klinicki bolnicki centar Zagreb, Zagreb, Hrvatska.

出版信息

Acta Med Croatica. 2009 Jun;63(3):237-44.

PMID:19827352
Abstract

Allogeneic hematopoietic progenitor cell (HPC) transplantation is an established therapy for many hematologic disorders. HPCs may be collected from bone marrow, peripheral blood, or umbilical cord blood. In order to minimize the risk for healthy HPC donors, thorough investigation is required before donation. The donor work-up should include medical history, physical examination, ECG, chest x-ray, blood count, coagulation screening, and testing for infectious disease markers. Donors should be fully informed on the donation procedure and sign an informed consent for donation. HPCs are traditionally collected from bone marrow with the donor in general anesthesia. The procedure includes multiple bone marrow aspirates from pelvic bones and at least overnight hospital stay. Although marrow donation is generally safe and well tolerated, minor complications like pain at the collection site, fatigue and pain on walking or sitting may occur in a relatively small proportion of donors (6%-20%). Major and life-threatening complications such as anesthesia-related events, mechanical injury to the bone, sacroiliac joint and sciatic nerve following marrow donation are relatively rare, being estimated to 0.1%-0.3% of cases. In the last decade, peripheral blood progenitor cells (PBPC) have become an increasingly used altemative to bone marrow. PBPC transplantation offers faster hematopoietic recovery and lower early transplant-related morbidity and mortality. The incidence of acute graft vs. host disease (GvHD) is no greater than in bone marrow transplants. However, there is evidence for increased chronic GvHD, which is in part related to the higher number of T and NK cells that are collected with PBPC and re-infused to the patient. Recombinant human granulocyte colony-stimulating factor (G-CSF) is used to mobilize PBPCs for collection by leukapheresis. Leukapheresis is usually perfomed after 4 to 5 days of G-CSF subcutaneous administration at a dose of 10 mg/kg b.w. Vascular access for apheresis may be accomplished by use of apheresis needle in antecubital vein. Placement of a double-lumen central apheresis catheter is rarely required in healthy donors. Citrate is the most commonly used anticoagulant for apheresis. One to three leukapheresis procedures are required to collect adequate graft. There is an interindividual variation in progenitor cell mobilization among healthy donors, with a subset of donors that do not exhibit effective CD34+ cell mobilization. Donor age and G-CSF schedule are the factors that significantly affect PBPC mobilization and collection in healthy donors. Procedures for mobilization and collection of PBPC from healthy donors are generally well tolerated. Common adverse reactions of G-CSF application include bone pain, myalgia, headache and fatigue. Beside these mild side effects, moderate to life-threatening complications are sporadically observed. Spontaneous splenic rupture, acute lung injury, acute iritis, severe pyogenic infections, and anaphylactoid reactions were reported in healthy donors after G-CSF administration. Adverse effects of apheresis for PBPC collection are the same as for other apheresis procedure and include complications related to venous access and citrate toxicity. Leukapheresis typically results in a lower platelet count, an effect that is exacerbated by the use of G-CSF, which has been documented to cause mild, reversible thrombocytopenia. Fewer side effects were noted in pediatric donors compared to adult donors. PBPC collection in pediatric donors is safe and desired PBPC yields are easily achieved. Theoretical concerns exist about the potentially increasing long-term risk of leukemia after G-CSF administration in healthy donors. Recently, a report of AML developing in a 62-year-old female donor 14 months after G-CSF-primed PBPC donation has been published. Whether G-CSF therapy contributed to the development of this cancer is unknown, but future studies should carefully follow the donors and report any similar event. According to currently available evidence, the risk of major late toxicities secondary to administration of G-CSF is minimal.

摘要

异基因造血祖细胞(HPC)移植是治疗多种血液系统疾病的成熟疗法。造血祖细胞可从骨髓、外周血或脐带血中采集。为将健康造血祖细胞供者的风险降至最低,捐赠前需要进行全面调查。供者检查应包括病史、体格检查、心电图、胸部X光、血常规、凝血筛查以及传染病标志物检测。应让供者充分了解捐赠程序并签署捐赠知情同意书。传统上,造血祖细胞是在供者全身麻醉的情况下从骨髓中采集的。该程序包括从骨盆进行多次骨髓穿刺,且供者至少需住院过夜。虽然骨髓捐赠总体上是安全的且耐受性良好,但相对较小比例(6%-20%)的供者可能会出现一些轻微并发症,如采集部位疼痛、疲劳以及行走或坐立时疼痛。诸如与麻醉相关的事件、骨髓捐赠后对骨骼、骶髂关节和坐骨神经的机械损伤等严重且危及生命的并发症相对较少,估计发生率为0.1%-0.3%。在过去十年中,外周血祖细胞(PBPC)已越来越多地成为骨髓的替代选择。外周血祖细胞移植可使造血恢复更快,且早期移植相关的发病率和死亡率更低。急性移植物抗宿主病(GvHD)的发生率不高于骨髓移植。然而,有证据表明慢性移植物抗宿主病有所增加,这部分与外周血祖细胞采集并重新输注给患者的T细胞和NK细胞数量较多有关。重组人粒细胞集落刺激因子(G-CSF)用于通过白细胞单采术动员外周血祖细胞进行采集。白细胞单采术通常在皮下给予剂量为10mg/kg体重的G-CSF 4至5天后进行。单采术的血管通路可通过在前臂静脉使用单采针来实现。健康供者很少需要放置双腔中心单采导管。枸橼酸盐是单采术中最常用的抗凝剂。需要进行一至三次白细胞单采程序以采集足够的移植物。健康供者之间的祖细胞动员存在个体差异,有一部分供者不会出现有效的CD34+细胞动员。供者年龄和G-CSF给药方案是显著影响健康供者外周血祖细胞动员和采集的因素。健康供者外周血祖细胞动员和采集的程序通常耐受性良好。应用G-CSF的常见不良反应包括骨痛、肌痛、头痛和疲劳。除了这些轻微副作用外,偶尔也会观察到中度至危及生命的并发症。有报道称健康供者在使用G-CSF后出现自发性脾破裂、急性肺损伤、急性虹膜炎、严重化脓性感染和类过敏反应。外周血祖细胞采集的单采术不良反应与其他单采程序相同,包括与静脉通路和枸橼酸盐毒性相关的并发症。白细胞单采术通常会导致血小板计数降低,使用G-CSF会加剧这种影响,已有文献证明G-CSF会导致轻度、可逆的血小板减少。与成年供者相比,儿科供者的副作用较少。儿科供者的外周血祖细胞采集是安全的,并且很容易获得理想的外周血祖细胞产量。对于健康供者使用G-CSF后白血病长期风险可能增加存在理论上的担忧。最近,有一篇关于一名62岁女性供者在接受G-CSF预处理的外周血祖细胞捐赠14个月后发生急性髓系白血病的报道发表。G-CSF治疗是否促成了这种癌症的发生尚不清楚,但未来的研究应仔细跟踪供者并报告任何类似事件。根据目前可得的证据,使用G-CSF继发的主要晚期毒性风险极小。

相似文献

1
[Collection of hematopoietic progenitor cells from healthy donors].[从健康供体采集造血祖细胞]
Acta Med Croatica. 2009 Jun;63(3):237-44.
2
The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation.细胞因子刺激的健康供体在异基因干细胞移植中的应用。
Haematologica. 2002 Aug;87(8 Suppl):35-41.
3
Efficacy and toxicity of a high-dose G-CSF schedule for peripheral blood progenitor cell mobilization in healthy donors.大剂量粒细胞集落刺激因子方案用于健康供体外周血祖细胞动员的疗效与毒性
Bone Marrow Transplant. 1999 Dec;24(12):1273-8. doi: 10.1038/sj.bmt.1702073.
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Mobilization and collection of peripheral blood progenitor cells for transplantation.用于移植的外周血祖细胞的动员与采集。
Transfus Apher Sci. 2005 Feb;32(1):63-72. doi: 10.1016/j.transci.2004.10.007.
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Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone.仅使用粒细胞集落刺激因子动员外周血干细胞期间健康供体发生的急性肺损伤。
Haematologica. 2005 Mar;90(3):ECR10.
6
Administration of erythopoietin and granulocyte colony-stimulating factor in donor/recipient pairs to collect peripheral blood progenitor cells (PBPC) and red blood cell units for use in the recipient after allogeneic PBPC transplantation.在供体/受体对中给予促红细胞生成素和粒细胞集落刺激因子,以采集外周血祖细胞(PBPC)和红细胞单位,用于异基因PBPC移植后的受体。
Haematologica. 2001 Nov;86(11):1209-18.
7
Rapid engraftment after allogeneic transplantation of density-enriched peripheral blood CD34+ cells in patients with advanced hematologic malignancies.晚期血液系统恶性肿瘤患者接受密度富集外周血CD34+细胞同种异体移植后的快速植入。
Cancer. 2001 Jun 15;91(12):2205-13.
8
Weighing the risks of G-CSF administration, leukopheresis, and standard marrow harvest: ethical and safety considerations for normal pediatric hematopoietic cell donors.权衡粒细胞集落刺激因子(G-CSF)给药、白细胞单采和标准骨髓采集的风险:正常儿科造血细胞供者的伦理和安全考量
Pediatr Blood Cancer. 2006 Apr;46(4):422-33. doi: 10.1002/pbc.20708.
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Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors.使用与患者匹配的正常儿科供者进行异基因外周血干细胞移植。
Bone Marrow Transplant. 1996 Nov;18(5):885-90.
10
PBPC collection techniques: standard versus large volume leukapheresis (LVL) in donors and in patients.外周血干细胞采集技术:供体及患者中的标准采集法与大容量白细胞单采术(LVL)
Transfus Apher Sci. 2005 Apr;32(2):167-76. doi: 10.1016/j.transci.2004.10.018.

引用本文的文献

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Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.异基因造血干细胞移植供者 G-CSF 动员期间的心理和身体副作用。
Ann Hematol. 2024 Aug;103(8):3199-3206. doi: 10.1007/s00277-024-05753-5. Epub 2024 Apr 19.
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Optimizing Stem Cells Mobilization Strategies to Ameliorate Patient Outcomes: A Review of Guide- lines and Recommendations.优化干细胞动员策略以改善患者预后:指南与建议综述
Int J Hematol Oncol Stem Cell Res. 2017 Jan 1;11(1):78-88.
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The policy statement of the American Academy of Pediatrics -- children as hematopoietic stem cell donors -- a proposal of modifications for application in the UK.
美国儿科学会的政策声明——儿童作为造血干细胞供者——对在英国应用的修改建议。
BMC Med Ethics. 2013 Oct 31;14:43. doi: 10.1186/1472-6939-14-43.
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Making the case for private cord blood banking: mission accomplished!: comment to Schmidt et al., Stem Cell Rev and Rep (2010) 6:234-236.为私人脐带血库辩护:任务完成!:对施密特等人的评论,《干细胞评论与报告》(2010年)6:234 - 236
Stem Cell Rev Rep. 2011 Sep;7(3):485-7. doi: 10.1007/s12015-010-9223-5.