Brugger W, Heimfeld S, Berenson R J, Mertelsmann R, Kanz L
Albert-Ludwigs University Medical Center, Department of Hematology/Oncology, Freiburg, Germany.
N Engl J Med. 1995 Aug 3;333(5):283-7. doi: 10.1056/NEJM199508033330503.
Autologous peripheral-blood progenitor cells can restore hematopoiesis after high-dose chemotherapy in patients with solid tumors or hematologic cancers. We investigated the ability of peripheral-blood progenitor cells generated ex vivo to restore hematopoiesis in patients with cancer who have undergone high-dose chemotherapy.
Ten patients who had received high-dose chemotherapy were given transplants of autologous progenitor cells that had been generated ex vivo. We used 11 million CD34+ hematopoietic progenitor cells as the starting population for the cell growth. This number corresponds to less than 10 percent of the usual preparation of peripheral-blood CD34+ mononuclear cells used in leukapheresis. The CD34+ cells were grown in medium containing autologous plasma, recombinant human stem-cell factor, interleukin-1 beta, interleukin-3, interleukin-6, and erythropoietin.
No toxic effects were observed with the infusion of the generated cells. The cells promoted a rapid and sustained hemopoietic recovery when transplanted after treatment with high-dose etoposide (1500 mg per square meter of body-surface area), ifosfamide (12 g per square meter), carboplatin (750 mg per square meter), and epirubicin (150 mg per square meter). The pattern of hematopoietic reconstitution was identical to that in historical controls treated with unseparated mononuclear cells or positively selected CD34+ cells.
A small number of peripheral-blood CD34+ cells, when grown ex vivo, can supply a population of hematopoietic precursors that have the ability to restore blood formation in patients treated with high doses of chemotherapy. This method, which requires only a small volume of the patient's blood, may reduce the risk of tumor-cell contamination, circumvent the need for leukapheresis, and allow repeated cycles of high-dose chemotherapy.
自体外周血祖细胞可在实体瘤或血液系统癌症患者接受大剂量化疗后恢复造血功能。我们研究了体外生成的外周血祖细胞在接受大剂量化疗的癌症患者中恢复造血功能的能力。
10例接受大剂量化疗的患者接受了体外生成的自体祖细胞移植。我们使用1100万个CD34+造血祖细胞作为细胞生长的起始群体。这个数量不到白细胞分离术中常用的外周血CD34+单核细胞制剂的10%。CD34+细胞在含有自体血浆、重组人干细胞因子、白细胞介素-1β、白细胞介素-3、白细胞介素-6和促红细胞生成素的培养基中生长。
输注生成的细胞未观察到毒性作用。在用大剂量依托泊苷（每平方米体表面积1500 mg）、异环磷酰胺（每平方米12 g）、卡铂（每平方米750 mg）和表柔比星（每平方米150 mg）治疗后移植时，这些细胞促进了快速且持续的造血恢复。造血重建模式与用未分离的单核细胞或阳性选择的CD34+细胞治疗的历史对照相同。
少量外周血CD34+细胞在体外生长时，可提供一群造血前体细胞，这些细胞有能力在接受高剂量化疗的患者中恢复血液生成。这种方法仅需患者少量血液，可能降低肿瘤细胞污染的风险，避免白细胞分离术的需要，并允许重复进行高剂量化疗周期。
