Dreger P, Haferlach T, Eckstein V, Jacobs S, Suttorp M, Löffler H, Müller-Ruchholtz W, Schmitz N
Second Department of Medicine, University of Kiel, Germany.
Br J Haematol. 1994 Jul;87(3):609-13. doi: 10.1111/j.1365-2141.1994.tb08321.x.
Allogeneic transplantation of peripheral blood progenitor cells (PBPC) makes the general anaesthesia of the donor unnecessary and may result in more rapid engraftment and faster recovery of the immune system. We have studied G-CSF-mediated PBPC mobilization in healthy donors and analysed the cellular composition of the resulting PBPC grafts. PBPC grafts were obtained from nine healthy donors (18-67 years old) for allogeneic or syngeneic transplantation. Six donors received 10 micrograms/kg G-CSF per day, the others 5-6 micrograms/kg. Mobilization and harvesting were well tolerated except for moderate bone pain which occurred in all donors primed with 10 micrograms/kg. With 10 micrograms/kg, a 31-fold (9-62) enrichment of circulating CD34+ cells was observed with peak values constantly occurring on day 5 after the start of G-CSF administration. Starting harvest on day 5, one to three collections on consecutive days yielded 5.5 x 10(6)/kg (0.9-10.7) CD34+ cells, 219 x 10(6)/kg (106-314) T cells, and 34 x 10(6)/kg (23-67) NK cells per 10 litres leukapheresis volume. Altogether, PBPC grafts contained 3 times more CD34+ cells, 7 times more T cells, and 20 times more NK cells than five allogeneic marrow grafts that were analysed for comparison. The yield of CD34+ cells per 10 litres apheresis volume as well as the height of the CD34+ peak in peripheral blood were inversely correlated to the age of the donor. In the donors primed with 5-6 micrograms/kg G-CSF the increase of circulating CD34+ cells (4-7-fold enrichment) and the CD34+ cell yield per 10 litres leukapheresis volume (1 x 10(6)/kg [0.8-2.2]) was much smaller compared with the 10 micrograms/kg group. In conclusion, sufficient amounts of PBPC capable of restoring haemopoiesis in allogeneic recipients can be mobilized safely by administration of G-CSF (10 micrograms/kg s.c. for 5 d) in healthy donors, and harvested with one or two leukapheresis procedures. Whether the large numbers of T-cells and NK cells that are contained in the collection products may influence graft-versus-host and graft-versus-leukaemia reactivities of PBPC grafts remains to be determined.
外周血祖细胞(PBPC)的异基因移植无需供者进行全身麻醉,且可能导致更快的植入和免疫系统更快恢复。我们研究了健康供者中粒细胞集落刺激因子(G-CSF)介导的PBPC动员情况,并分析了由此获得的PBPC移植物的细胞组成。PBPC移植物取自9名健康供者(年龄18 - 67岁)用于异基因或同基因移植。6名供者每天接受10微克/千克的G-CSF,其他供者接受5 - 6微克/千克。除了所有接受10微克/千克预处理的供者均出现的中度骨痛外,动员和采集耐受性良好。使用10微克/千克时,观察到循环CD34+细胞富集31倍(9 - 62倍),峰值持续出现在G-CSF给药开始后的第5天。从第5天开始采集,连续1 - 3天采集,每10升白细胞分离术采集量可获得5.5×10⁶/千克(0.9 - 10.7)个CD34+细胞、219×10⁶/千克(106 - 314)个T细胞和34×10⁶/千克(23 - 67)个NK细胞。总体而言,PBPC移植物中CD34+细胞比用于比较分析的5份异基因骨髓移植物多3倍,T细胞多7倍,NK细胞多20倍。每10升单采量中CD34+细胞的产量以及外周血中CD34+峰值高度与供者年龄呈负相关。在接受5 - 6微克/千克G-CSF预处理的供者中,循环CD34+细胞的增加(4 - 7倍富集)以及每10升白细胞分离术采集量中CD34+细胞产量(1×10⁶/千克[0.8 - 2.2])与10微克/千克组相比要小得多。总之,通过对健康供者给予G-CSF(10微克/千克皮下注射,共5天),能够安全地动员出足够数量的可在异基因受者中恢复造血的PBPC,并通过一或两次白细胞分离术进行采集。采集产物中所含大量T细胞和NK细胞是否会影响PBPC移植物的移植物抗宿主反应和移植物抗白血病反应仍有待确定。