Bojanić Ines, Cepulić Branka Golubić, Mazić Sanja
Zavod za klinicku transfuziologiju, Klinicki zavod za laboratorijsku dijagnostiku, Klinicki bolnicki centar Zagreb, Zagreb, Hrvatska.
Acta Med Croatica. 2009 Jun;63(3):237-44.
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.
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。