Körbling M, Giralt S, Khouri I, Mirza N, Donato M, Anderlini P, Fischer H, Andreeff M, McMannis J, Champlin R
The University of Texas M.D. Anderson Cancer Center, Division of Medicine, Department of Blood and Marrow Transplantation, Houston, Texas 77030, USA.
J Clin Apher. 2001;16(2):82-7. doi: 10.1002/jca.1017.
Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3(+), CD3(+)4(+), CD3(+)8(+), CD19(+), CD3(-)56(+)16(+), and CD34(+) cells contained in apheresis products from 61 consecutive non-cytokine treated, human leukocyte antigen (HLA)-matched donors for lymphocyte collection with the corresponding apheresis-derived cell yield from 112 consecutive, HLA-matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) 6 microg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG-CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG-CSF treated product yields exceeding untreated product yields by a median of 2.1-fold (range: 1.3-2.6). However, the CD34(+) cell yield in rhG-CSF-treated apheresis products exceeded untreated products by 26-fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 x 10(8)/kg CD3(+) cells. Untreated apheresis products contained a median of 0.2 x 10(6)/kg CD34(+) cells. A potential engraftment dose of > or =0.5 x 10(6) CD34(+) cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3(+) cells for adoptive immunotherapy. Compared with that of an rhG-CSF stimulated apheresis product, the CD34(+) cell count is usually, but not always, below the engraftment dose range. RhG-CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34(+) cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and/or Flt-3 Ligand can immunomodulate allotransfusates in vivo to improve the graft-vs.-leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft-vs.-host disease (GVHD).
供体淋巴细胞输注作为一种过继性细胞免疫疗法，用于预防或治疗异基因干细胞移植后的复发，已引起了广泛关注。本研究旨在比较61例连续的未接受细胞因子治疗、人类白细胞抗原（HLA）匹配的淋巴细胞采集供体的单采产品中所含的CD3(+)、CD3(+)4(+)、CD3(+)8(+)、CD19(+)、CD3(-)56(+)16(+)和CD34(+)细胞的产量，与112例连续的、HLA匹配的接受重组人粒细胞集落刺激因子（rhG-CSF，非格司亭）治疗的血干细胞采集供体的相应单采来源细胞产量。rhG-CSF治疗方案为每12小时皮下注射6 μg/kg，直至完成细胞采集。单采在rhG-CSF治疗的第4天或第5天开始。两个样本组中淋巴细胞亚群的产量有显著差异，rhG-CSF治疗组产品产量比未治疗组产品产量中位数高出2.1倍（范围：1.3 - 2.6）。然而，rhG-CSF治疗的单采产品中CD34(+)细胞产量比未治疗组高出26倍。一次未治疗的单采程序通常足以采集到目标剂量的1×10(8)/kg CD3(+)细胞。未治疗的单采产品中CD34(+)细胞中位数为0.2×10(6)/kg。57份未治疗的单采产品中有16%含有每千克受体体重≥0.5×10(6)个CD34(+)细胞的潜在植入剂量。在正常、未治疗的供体中进行一次单采就能为过继性免疫治疗提供足够数量的CD3(+)细胞。与rhG-CSF刺激的单采产品相比，CD34(+)细胞计数通常（但并非总是）低于植入剂量范围。rhG-CSF治疗对单采采集的淋巴细胞亚群产量影响不大，但对CD34(+)细胞的释放具有高度选择性。本报告为相关研究提供了基线数据，这些研究将表明其他细胞因子，如粒细胞巨噬细胞集落刺激因子（GM-CSF）和/或Flt-3配体是否能在体内对同种异体输血产物进行免疫调节，以提高异基因干细胞移植后的移植物抗白血病（GVL）效应，同时降低移植物抗宿主病（GVHD）的发生率和严重程度。
