Hénon P H, Sovalat H, Bourderont D
Department of Hematology, CHM, Mulhouse, France.
J Biol Regul Homeost Agents. 2001 Jan-Mar;15(1):62-7.
Over the years, various biological parameters have been proposed for predicting rapidity and long term maintenance of hematopoietic engraftment after peripheral blood stem cell transplantation (PBSCT). Determination of the graft content in CFU-GM was the only one available until the end of the eighties. But, for technical reasons, and also because it does not actually evaluate the self-renewal potential of the cell products reinfused, it has now been commonly replaced by the determination of CD34+ cell amounts, which are known to contain the pluripotent hematopoietic stem cells. However, a frequent discrepancy still exists between the number of CD34+ cells reinfused and the engraftment efficiency. We have recently demonstrated a higher accuracy of the numbers of CD34+38- cells contained in graft products to predict rapidity of trilineage engraftment, which has further been confirmed by other investigators. Furthermore, we and others, have proposed a threshold dose of 5 x 10(4) CD34+38- cells/kg b.w. below which the trilineage engraftment kinetics are significantly slower and unpredictible. This "cut-off" value also appears to be a realistic clinical tool to decide if hematopoietic growth factor(s) must be administered or not after PBSCT. Indeed, when for example, rh-G-CSF administration after transplant of CD34+38- amounts < 5 x 10(4) kg has indisputable positive effects on the rapidity of neutrophil engraftment, length of hospitalization and posttransplant costs, enough to make it fully justified in this situation, it is absolutely not the case when it is administered after reinfusion of CD34+38- cell amounts > 5 x 10(4) /kg. In this case, posttransplant rh-G-CSF administration could even result in a decrease in stem cells with self-renewal potential of the graft, which should still raise more concerns for its indiscriminate and costly use.
多年来,人们提出了各种生物学参数来预测外周血干细胞移植(PBSCT)后造血植入的速度和长期维持情况。直到80年代末,CFU-GM中移植物含量的测定是唯一可用的方法。但由于技术原因,也因为它实际上并未评估回输细胞产物的自我更新潜力,现在它已普遍被CD34+细胞数量的测定所取代,因为已知CD34+细胞包含多能造血干细胞。然而,回输的CD34+细胞数量与植入效率之间仍经常存在差异。我们最近证明,移植物产品中所含CD34+38-细胞数量在预测三系植入速度方面具有更高的准确性,其他研究人员也进一步证实了这一点。此外,我们和其他人提出了5×10⁴个CD34+38-细胞/千克体重的阈值剂量,低于该剂量,三系植入动力学明显较慢且不可预测。这个“临界值”似乎也是一个现实的临床工具,可用于决定PBSCT后是否必须给予造血生长因子。事实上,例如,当移植的CD34+38-数量<5×10⁴/千克后给予重组人粒细胞集落刺激因子(rh-G-CSF),对中性粒细胞植入速度、住院时间和移植后费用有无可争议的积极影响,足以使其在这种情况下完全合理,但当在回输CD34+38-细胞数量>5×10⁴/千克后给予时,情况绝对并非如此。在这种情况下,移植后给予rh-G-CSF甚至可能导致移植物中具有自我更新潜力的干细胞减少,这仍然应该引起人们对其滥用和昂贵使用的更多关注。