TRANSPLANTATION OF ALLOGENEIC PERIPHERAL-BLOOD STEM-CELLS MOBILIZED BY RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR
TRANSPLANTATION OF ALLOGENEIC PERIPHERAL-BLOOD STEM-CELLS MOBILIZED BY RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR
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DOI：
10.1182/blood.v85.6.1655.bloodjournal8561655
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发表时间：
1995-03-15
期刊：
影响因子：
20.3
通讯作者：
BUCKNER, CD
中科院分区：
文献类型：
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作者：
BENSINGER, WI;WEAVER, CH;BUCKNER, CD
外周血干细胞(PBSCs)因其易于采集和快速造血重建而被广泛应用于自体移植。然而，由于担心细胞因子注射对供者的毒性，以及理论上大量输注T细胞会增加移植物抗宿主病(GVHD)的风险，PBSC很少被用于异基因移植。8名晚期恶性肿瘤患者接受了来自基因分型相同的兄弟姐妹捐赠者的异基因PBSC移植。所有供者均皮下注射重组人粒细胞集落刺激因子(rhG-CSF，16mU/kg/d)5d后去白细胞2d。患者接受全身照射后加用环磷酰胺(n=7)或依托泊苷、硫替巴治疗。和环磷酰胺组(n=1)，采集后立即输注PBSCs，不加修饰。所有患者均接受环孢素+甲氨蝶呤(n=6)或泼尼松(n=2)预防GVHD。重组人粒细胞集落刺激因子耐受性良好，两名供者出现轻度骨痛，需要使用扑热息痛。所有患者均移植成功，其中7例患者在移植后第18天达到中性粒细胞500个/亩L，第12天达到20,000个/亩L。4对性别不合的供受者进行Y染色体分析，2对性别匹配的供受者进行DNA分析，证实供者完全植入。1名患者于移植后第18天死于肝静脉闭塞症，但尚未进行染色体分析(1名患者的结果待定)。另一名患者在移植后78天死于真菌感染。急性移植物抗宿主病2例，移植物抗宿主病3级1例。1名患者移植后301天慢性移植物抗宿主病缓解；其余5名患者在移植后67至112天内存活且无疾病。初步结果表明，用rhG-CSF动员的异基因PBSC可以提供快速的血液学恢复，而急性GVHD的发生率比骨髓动员的要高得多。需要进一步的随访来确定慢性移植物抗宿主病的发生率以及移植后复发的任何潜在的有益影响。(C)1995年由美国血液病学会主办。
Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft-versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 mu g/ kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa. and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis. rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/mu l achieved by day 18 and 20,000 platelets/mu L by day 12. Complete donor engraftment was documented by Y chromosome analysis in ail four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further followup is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant. (C) 1995 by The American Society of Hematology.