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烷基溶血磷脂对人外周血祖细胞的化学净化作用及其对大剂量治疗后造血恢复的影响

Chemopurging of peripheral blood-derived progenitor cells by alkyl-lysophospholipid and its effect on haematopoietic rescue after high-dose therapy.

作者信息

Koenigsmann M P, Notter M, Knauf W U, Papadimitriou C A, Oberberg D, Reufi B, Mücke C, Thiel E, Berdel W E

机构信息

Department of Internal Medicine, Benjamin Franklin Hospital, Free University of Berlin, Germany.

出版信息

Bone Marrow Transplant. 1996 Sep;18(3):549-57.

PMID:8879616
Abstract

One reason for relapse after high-dose tumor therapy with subsequent autologous stem cell transplantation is tumor cell contamination of the graft. Removal of tumor cells from bone marrow grafts by chemopurging with the ether lipid edelfosine has been established as an effective and simple method. When compared with bone marrow derived grafts, progenitor cells from peripheral blood have considerably reduced the haematological recovery times. However, this advantage is put at risk by the nonspecific haematotoxic activity of the purging agent. We therefore compared the in vitro recovery of peripheral blood derived progenitor cells (PBPC) from either non-purged (n = 41) or purged (75 micrograms/ml of ether lipid for 4 h at 37 degrees C, n = 48) leukapheresis products. The recovery of CFU-GM after cryopreservation was 63 +/- 4% without and 48 +/- 3% with purging (P = 0.007). After high-dose therapy, patients (n = 37) received similar amounts of either non-purged (n = 17) or purged (n = 20) autologous PBPC. The median haematological recovery times (non-purged vs purged) to > 500 WBC/microlitres were 9.0 vs 8.5 days after transplantation, to > 2000 PMN/microlitres 10.5 vs 10.0 days, and to > 50,000 PLT/microlitres 15.5 vs 14.0 days. All differences were statistically not significant. We conclude that ether lipid purging of PBPC leads to a significant, however tolerable loss of progenitor cells in vitro, and that haematological recovery times after high-dose therapy are identically short, provided similar amounts of PBPC are reinfused.

摘要

高剂量肿瘤治疗后继以自体干细胞移植后复发的一个原因是移植物中存在肿瘤细胞污染。通过用醚脂依地福新进行化学净化从骨髓移植物中去除肿瘤细胞已被确立为一种有效且简便的方法。与骨髓来源的移植物相比,外周血祖细胞显著缩短了血液学恢复时间。然而,这种优势因净化剂的非特异性血液毒性活性而受到威胁。因此,我们比较了未净化(n = 41)或净化(在37℃下用75微克/毫升醚脂处理4小时,n = 48)的白细胞分离产物中外周血来源祖细胞(PBPC)的体外恢复情况。冷冻保存后CFU - GM的回收率在未净化时为63±4%,净化后为48±3%(P = 0.007)。高剂量治疗后,患者(n = 37)接受了相似数量的未净化(n = 17)或净化(n = 20)的自体PBPC。移植后白细胞计数>500/微升时的中位血液学恢复时间(未净化组与净化组)分别为9.0天和8.5天,中性粒细胞计数>2000/微升时为10.5天和10.0天,血小板计数>50,000/微升时为15.5天和14.0天。所有差异均无统计学意义。我们得出结论,PBPC的醚脂净化在体外会导致祖细胞显著但可耐受的损失,并且如果回输相似数量的PBPC,高剂量治疗后的血液学恢复时间同样较短。

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