Cesaro Simone, Marson Piero, Gazzola Maria Vittoria, De Silvestro Giustina, Destro Roberta, Pillon Marta, Calore Elisabetta, Messina Chiara, Zanesco Luigi
Clinic of Pediatric Oncology-Hematology, Department of Pediatrics, University of Padova, via Giustiniani 3, 35128 Padua, Italy.
Haematologica. 2002 Aug;87(8 Suppl):35-41.
Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
用重组人粒细胞集落刺激因子（rhG-CSF）治疗健康供者，可使足够数量的CD34+细胞动员并外周化进入循环血液，随后可通过白细胞分离术（外周血干细胞采集）进行采集。该程序避免了骨髓采集的侵入性以及与全身麻醉相关的风险。rhG-CSF的主要不良反应为：骨痛，84%；头痛，54%；疲劳，31%；恶心，13%，供者通常将这些不良反应评为中度至重度，在停用细胞因子后2 - 3天内缓解。镇痛药，主要是对乙酰氨基酚，足以控制疼痛。不到5%的供者会出现非心源性胸痛、注射部位局部反应、失眠、头晕或低热。因rhG-CSF或白细胞分离术的不良反应而停止外周血干细胞采集程序的情况很少见（0.5%），但在5% - 20%的病例中，由于需要足够的静脉通路（这需要插入中心静脉或静脉导管），良好的耐受性可能会受到影响。对于用rhG-CSF刺激健康供者没有绝对禁忌证，但非创伤性脾破裂、虹膜炎、心脏缺血和痛风性关节炎病例的描述表明，在决定外周血干细胞采集的合格性时，进一步的预防性限制是可取的。接受异基因外周血干细胞移植的患者的主要优势是血液学和免疫恢复更快，以及通过降低移植相关死亡率在晚期疾病中可能具有更大的疗效。关于在无关健康供者中使用rhG-CSF的一个主要担忧是其在引发恶性肿瘤，特别是骨髓增生异常综合征和急性髓系白血病方面可能发挥的作用存在不确定性。目前尚无足够样本量和随访的研究能够回答这个问题，但最近的两项回顾性研究报告称，从中期来看，rhG-CSF与淋巴增殖性疾病的增加无关。目前，对在健康供者中使用rhG-CSF的长期安全性仍需谨慎，但就供者G-CSF刺激的良好中短期耐受性以及对白血病患者的潜在主要疗效而言，目前积累的数据令人鼓舞。
