脐血复温后细胞输入剂量对植入的预测作用分析

Analysis of Post-thaw Infused Cell Dose for Predicting Engraftment after Unrelated Cord Blood Transplantation

本研究探讨非血缘供者脐带血移植(unrelated cord blood transplantation,UCBT)中复温后供者细胞输入剂量对植入和造血重建的预测作用。回顾性分析1999年8月至2010年4月间接受单份UCBT的97例儿童恶性及非恶性疾病患者的临床资料,比较冷冻前和复温后检测的总有核细胞(total nucleated cells,TNC)、CD34+细胞及粒-巨噬细胞集落形成单位(colony-forming unit-granulocyte-macrophage,CFU-GM)的输入剂量对受者的植入及造血重建速度的影响,供者脐带血均来自广州脐血库。结果表明,冷冻前TNC(/kg)(mean±SD:7.65×107±4.26×107;median:6.34×107)、CD34+细胞(/kg)(mean±SD:4.64×105±4.47×105;median:3.03×105)及CFU-GM(/kg)(mean±SD:0.79×105±1.09×105;median:0.57×105)与其对应的复温后TNC(/kg)(mean±SD:6.98×107±4.12×107;median:6.00×107)、CD34+(/kg)(mean±SD:6.86×105±8.56×105;median:4.17×105)、CFU-GM(/kg)(mean±SD:0.52×105±0.52×105;Median:0.39×105)均显著相关(r=0.952,p<0.001;r=0.794,p<0.001;r=0.478,p<0.001)。植入组(n=70)的冷冻前和复温后CFU-GM输入剂量均高于未植入组(n=22)(p=0.023;p=0.011),而二者的冷冻前和复温后的TNC、CD34+细胞输入量的差异无统计学意义。冷冻前TNC、CD34+细胞、CFU-GM输入剂量与受者的中性粒细胞植入时间呈负相关(r=-0.285,p=0.018;r=-0.396,p=0.002;r=-0.373,p=0.002),复温后TNC与CD34+细胞数亦与之呈负相关(r=-0.260,p=0.031;r=-0.483,p<0.001),而只有冷冻前CD34+细胞数与血小板植入时间负相关(r=-0.352,p=0.013)。结论 :CFU-GM输入剂量对预测植入有一定帮助,而冷冻前和复温后的各项指标相比,前者与植入及造血重建速度的相关性更为密切,提示脐带血在提供搜寻或发放用于移植之前,完善相应的造血功能检测是非常必要的。

This study was purposed to investigate the role of post-thaw infused donor cells for predicting engraftment and hematopdietic reconstitution after unrelated cord blood transplantation （UCBT）. The retrospective analysis was performed on clinical data of 97 children with malignant or non-malignant diseases received single unit UCBT from August 1999 to April 2010. The impact of pre-freezing and post-thaw cell dose of total nucleated cells （ TNC）, CD34＋ cells and colony-forming units-granulocyte/macrophage （CFU-GM） on engraftment and hematological recovery after UCBT was analyzed. Unrelated donors were from Guangzhou cord blood bank （GZCBB） entirely. The results indicated that the pre-freezing TNC （/kg） （mean ± SD： 7.65 ×10^7 ＋ 4.26 ×10^7 ; median： 6.34 ×10^7 ）, CD34 ＋ cells （/kg） （mean±SD： 4.64×10^5± 4.47×10^5; median： 3.03x105） andCFU-GM （/kg） （mean±SD： 0.79×10^5 el.09x 105; median： 0.57 x 105） showed a good correlation with their post-thaw counterparts including TNC（/kg） （mean ± SD： 6.98 ×10^7 ± 4.12×10^7 ; median： 6.00 ×10^7） ,CD34 ＋cells （/kg） （Mean ± SD ：6.86×10^5＋ 8.56 ×10^5 ;Median： 4.17 ×10^5） , and CFU-GM （/kg） （mean ±SD： 0.52 ×10^5 ±0.52 ×10^5; median： 0.39 ×10^5） （r=0.952, p 〈0.001; r = 0. 794, p 〈 0. 001 ; r = 0. 478, p 〈 0. 001 ）. Either the pre-freezing or post-thaw number of infused CFU-GM was significant higher in patients who achieved engraftment （ n = 70 ） than those who suffered graft failure （ n = 22 ） （ p = 0. 023 and 0.011, respectively）, but no significant difference of TNC and CD34＋ cells dose （ pre-freezing or post-thaw） were found between these two groups. Pre-freezing CFU-GM, TNC, CD34＋ cell dose negatively correlated with the time of neutrophil engraftment （ r = - 0. 285, p = 0. 018 ; r = - 0. 396, p = 0. 002 ; r = - 0. 373, p = 0. 002）, as well as the post-thaw number of TNC and CD34 ＋ cells （r = -0. 260, p = 0. 031 ; r = -0. 483, p 〈 0. 001 ）, whereas only prefreezing CD34 ＋ cells showed a significant correlation with platelet engraftment time （ r =- 0. 352, p = 0. 013 ）. It is concluded that the CFU-GM amount is useful for predicting engraftment of UCBT, while pre-freezing hematopoietic cell doses show superior correlation with the speed of engraftment and hematopoietic reconstitution than their post-thaw counterparts in pediatric recipients, suggesting that it is essential to perform hematopoietic potency assay on each cord blood unit prior to listing or release for administration.