Hassan H T, Stockschläder M, Schleimer B, Krüger W, Zander A R
Bone Marrow Transplantation Center, Hamburg University Hospital Eppendorf, Germany.
Transpl Immunol. 1996 Dec;4(4):319-23. doi: 10.1016/s0966-3274(96)80054-2.
Recombinant human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem/progenitor cells (PBPC) have replaced bone marrow (BM) harvests for autologous transplantation after myeloablative therapy in cancer patients. G-CSF-mobilized PBPC from healthy donors contain one log excess of T lymphocytes representing a potential risk for graft-versus-host disease (GVHD). However, recent pilot clinical studies of G-CSF-mobilized allogeneic PBPC transplantation have shown rapid haematological recovery and no severe acute GVHD except in a very few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected during the pioneering period of allogeneic PBPC transplantation. The present study was performed to address the possible reasons for the rapid haematological recovery and the absence of severe acute GVHD observed after allogeneic PBPC transplantation by comparing the contents and subsets of CD3+ and CD34+ G-CSF-mobilized PBPC (n = 31) with those of BM (n = 26) allografts from healthy adult donors. The present results revealed that the phenotypic profiles of CD3+ and CD34+ cells differ between PBPC and BM allografts. The single PBPC leukapheresis product contained 10 times more mononuclear cells, 1.5 times more CD34+ cells, 5.5 times more CD3+ T lymphocytes, 3 times more CD19+ B lymphocytes and 3.8 times more CD14+ monocytes than the single BM harvest. Both CD34+CD33+ myeloid progenitor cells and CD34+HLA-DR-long-term reconstituting haemopoietic stem cells were significantly increased in the CD34+ G-CSF-mobilized PBPC compared with the CD34+ BM cells; median 73.1% and 30.4% vs 60.6% and 5.0%, respectively, P < 0.01. The percentage of CD3+ cells coexpressing CD4 (T helper/inducer) was similar in both PBPC and BM allografts, 47.2% and 45.6%, respectively, whereas the percentage of CD3+ cells coexpressing CD8 (T suppressor/cytotoxic) was significantly decreased in PBPC compared with BM; 37.0% vs 55.9%, p < 0.01. The rapid haematological recovery after allogeneic PBPC transplantation could be due to the increased content of CD34+CD33+ myeloid committed cells and the CD34+HLA-DR-long-term reconstituting haemopoietic stem cells in the PBPC allografts. Also, the absence of an increased risk of severe acute GVHD after allogeneic PBPC transplantation could be due to the increased T lymphocyte ratio of CD4+/CD8+ in the PBPC allografts. In conclusion, rapid haematological recovery without an increased risk of severe acute GVHD can be achieved using G-CSF-mobilized PBPC rather than BM for allogeneic transplantation.
重组人粒细胞集落刺激因子（G-CSF）动员的外周血干细胞/祖细胞（PBPC）已取代骨髓（BM）采集物，用于癌症患者清髓性治疗后的自体移植。来自健康供体的G-CSF动员的PBPC含有比正常多1个对数级的T淋巴细胞，这代表了移植物抗宿主病（GVHD）的潜在风险。然而，最近关于G-CSF动员的异基因PBPC移植的初步临床研究表明，血液学恢复迅速，除极少数病例外，无严重急性GVHD。因此，诱导严重急性GVHD的风险并不像异基因PBPC移植开创期预期的那么高。本研究旨在通过比较健康成年供体的G-CSF动员的PBPC（n = 31）和BM（n = 26）同种异体移植物中CD3+和CD34+细胞的含量及亚群，探讨异基因PBPC移植后血液学快速恢复以及无严重急性GVHD的可能原因。目前的结果显示，PBPC和BM同种异体移植物中CD3+和CD34+细胞的表型特征不同。单次PBPC白细胞分离产物中的单核细胞比单次BM采集物多10倍，CD34+细胞多1.5倍，CD3+T淋巴细胞多5.5倍，CD19+B淋巴细胞多3倍，CD14+单核细胞多3.8倍。与CD34+BM细胞相比，CD34+G-CSF动员的PBPC中CD34+CD33+髓系祖细胞和CD34+HLA-DR长期重建造血干细胞均显著增加；中位数分别为73.1%和30.4%，而CD34+BM细胞分别为60.6%和5.0%，P < 0.01。在PBPC和BM同种异体移植物中，共表达CD4（辅助性/诱导性T细胞）的CD3+细胞百分比相似，分别为47.2%和45.6%，而与BM相比，PBPC中共表达CD8（抑制性/细胞毒性T细胞）的CD3+细胞百分比显著降低；分别为37.0%和55.9%，p < 0.01。异基因PBPC移植后血液学的快速恢复可能归因于PBPC同种异体移植物中CD34+CD33+髓系定向细胞和CD34+HLA-DR长期重建造血干细胞含量的增加。此外，异基因PBPC移植后严重急性GVHD风险未增加可能归因于PBPC同种异体移植物中CD4+/CD8+T淋巴细胞比例的增加。总之，使用G-CSF动员的PBPC而非BM进行异基因移植可实现血液学快速恢复且不增加严重急性GVHD的风险。
