Menéndez Pablo, Pérez-Simón Jose A, Mateos Maria V, Caballero Maria D, González Marcos, San-Miguel Jesus F, Orfao Alberto
Servicio General de Citometría, Departamento de Medicina and Centro de Investigaciones del Cáncer, Universidad de Salamanca, Spain.
Br J Haematol. 2002 Oct;119(1):135-43. doi: 10.1046/j.1365-2141.2002.03794.x.
Currently, no information is available regarding the influence of the different CD34+ cell subsets infused on the haematopoietic recovery, following non-myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). We have explored, in a group of 13 patients receiving non-myeloablative allo-PBSCT from human leucocyte antigen-identical sibling donors, the influence of the total dose of CD34+ haematopoietic progenitor cells (HPC) infused, compared with that of the different CD34+ HPC and CD34- leucocyte subsets in the leukapheresis samples, on both engraftment and clinical outcome. The overall numbers of total CD34+ HPC (P = 0.002) and myelomonocytic-committed CD34+ HPC infused (P = 0.0002) were strongly associated with neutrophil recovery (> 1 x 109 neutrophils/l), the latter being the only independent parameter influencing neutrophil recovery. Regarding long-term engraftment, only the number of immature CD34+ HPC infused/kg correlated with the duration of hospitalization in the first 2 years after discharge (r = -0.75, P = 0.005). Both the overall amount of CD34+ HPC and the number of myelomonocytic CD34+ HPC infused showed a significant influence on the risk of graft-versus-host disease (GVHD). Thus, the overall probability of GVHD was 100%vs 25% for patients receiving >/= 5 x 106 CD34+ HPC or >/= 3.5 x 106 of myelomonocytic-committed CD34+ HPC vs lower doses (P = 0.013). None of the other CD34+ and CD34- cell subsets analysed correlated with development of GVHD. In summary, our results suggest that in non-myeloablative allo-PBSCT, high numbers of CD34+ HPC, especially the myelomonocytic-committed CD34+ progenitors, lead to rapid neutrophil engraftment. However, they also strongly impair clinical outcome by increasing the incidence of GVHD.
目前,关于非清髓性异基因外周血干细胞移植(allo - PBSCT)后输注不同的CD34⁺细胞亚群对造血恢复的影响尚无相关信息。我们在一组13例接受来自人类白细胞抗原相同的同胞供者的非清髓性allo - PBSCT的患者中,探讨了输注的CD34⁺造血祖细胞(HPC)总剂量,与白细胞分离样本中不同的CD34⁺HPC和CD34⁻白细胞亚群相比,对植入和临床结局的影响。输注的总CD34⁺HPC总数(P = 0.002)和髓单核细胞定向的CD34⁺HPC数量(P = 0.0002)与中性粒细胞恢复(> 1×10⁹中性粒细胞/升)密切相关,后者是影响中性粒细胞恢复的唯一独立参数。关于长期植入,仅每千克输注的未成熟CD34⁺HPC数量与出院后头2年的住院时间相关(r = -0.75,P = 0.005)。输注的CD34⁺HPC总量和髓单核细胞CD34⁺HPC数量均对移植物抗宿主病(GVHD)风险有显著影响。因此,接受≥5×10⁶个CD34⁺HPC或≥3.5×⁶个髓单核细胞定向的CD34⁺HPC的患者与较低剂量患者相比,GVHD的总体概率分别为100%和25%(P = 0.013)。分析的其他CD34⁺和CD34⁻细胞亚群均与GVHD的发生无关。总之,我们的结果表明,在非清髓性allo - PBSCT中,大量的CD34⁺HPC,尤其是髓单核细胞定向的CD34⁺祖细胞,可导致中性粒细胞快速植入。然而,它们也会因增加GVHD的发生率而严重损害临床结局。