Körbling M, Przepiorka D, Huh Y O, Engel H, van Besien K, Giralt S, Andersson B, Kleine H D, Seong D, Deisseroth A B
Section of Bone Marrow Transplantation, U.T.M.D. Anderson Cancer Center, Houston 77030.
Blood. 1995 Mar 15;85(6):1659-65.
Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.
由于担心移植物失败和移植物抗宿主病（GVHD），外周血干细胞（PBSCs）很少用于异基因移植。我们评估了9例难治性白血病或淋巴瘤患者接受清髓性治疗后，再接受来自 HLA 匹配同胞供体的异基因 PBSC 移植（allo - PBSCT）的结果。3例患者在异基因骨髓移植（allo - BMT）后11至21个月复发，随后使用相同供体进行 allo - PBSCT。6例患者将 PBSCs 作为其首次异基因移植。从供体采集经非格司亭动员的 PBSCs，进行3至4次单采并冷冻保存。单采采集物中，有核细胞计数中位数为16.5×10⁸/kg（范围为10.8至28.7×10⁸），CD34⁺细胞为10.7×10⁶/kg（范围为7.5至22.5×10⁶），CD3⁺细胞为300.0×10⁶/kg（范围为127.8至1523.2×10⁶）。冷冻、解冻和洗涤后，CD34⁺祖细胞的回收率中位数为106.4%（范围为36.7%至132.0%）。所有患者移植后直至植入均接受非格司亭治疗，环孢素和甲泼尼龙用于预防GVHD。中性粒细胞恢复至大于0.5×10⁹/L和大于1.0×10⁹/L的时间中位数分别为移植后9天（范围为8至10天）和9天（范围为8至11天），这与allo - BMT和粒细胞集落刺激因子治疗后的历史对照相似。血小板恢复至大于20×10⁹/L和大于50×10⁹/L的时间中位数分别为12天（范围为8至25天）和15天（范围为11至59天），明显快于对照组（P <.01）。通过细胞遗传学、荧光原位杂交和/或限制性片段长度多态性记录供体细胞植入情况，最长随访时间为283 +天。3例患者发生2级急性GVHD，仅累及皮肤。5例可评估患者中有3例显示有局限性慢性GVHD。冷冻保存的、经非格司亭刺激的异基因PBSCs可能是异基因骨髓移植的合适替代物，其优点是血小板恢复更快。尽管输注的CD3细胞比骨髓同种异体移植多1个对数，但急性GVHD很轻微。需要进一步研究来评估慢性GVHD的长期风险。
