Li Pira Giuseppina, Malaspina David, Girolami Elia, Biagini Simone, Cicchetti Elisabetta, Conflitti Gianpiero, Broglia Manuel, Ceccarelli Stefano, Lazzaro Stefania, Pagliara Daria, Meschini Antonella, Bertaina Alice, Montanari Mauro, Locatelli Franco
Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Biol Blood Marrow Transplant. 2016 Nov;22(11):2056-2064. doi: 10.1016/j.bbmt.2016.08.006. Epub 2016 Aug 9.
HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Because graft-versus-host diseases (GVHD) is a major complication of HLA-haploidentical HSCT because of alloreactive T cells in the graft, different methods have been used for ex vivo T cell depletion. Removal of donor αβ T cells, the subset responsible for GVHD, and of B cells, responsible for post-transplantation lymphoproliferative disorders, have been recently developed for HLA-haploidentical HSCT. This manipulation preserves, in addition to CD34 progenitors, natural killer, γδ T, and monocytes/dendritic cells, contributing to anti-leukemia activity and protection against infections. We analyzed depletion efficiency and cell yield in 200 procedures performed in the last 3 years at our center. Donors underwent CD34 hematopoietic stem cell (HSC) peripheral blood mobilization with granulocyte colony-stimulating factor (G-CSF). Poor CD34 cell mobilizers (48 of 189, 25%) received plerixafor in addition to G-CSF. Aphereses containing a median of 52.5 × 10 nucleated cells and 494 × 10 CD34 HSC were manipulated using the CliniMACS device. In comparison to the initial product, αβ T cell depletion produced a median 4.1-log reduction (range, 3.1 to 5.5) and B cell depletion led to a median 3.4-log reduction (range, 2.0 to 4.7). Graft products contained a median of 18.5 × 10 CD34 HSC/kg recipient body weight, with median values of residual αβ T cells and B cells of 29 × 10/kg and 33 × 10/kg, respectively. Depletion efficiency monitored at 6-month intervals demonstrated steady performance, while improved recovery of CD34 cells was observed after the first year (P = .0005). These data indicate that αβ T cell and B cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible.
对于需要进行异基因造血干细胞移植(HSCT)的儿童而言,HLA单倍型相同的家族供体是一种宝贵的选择。由于移植物中同种反应性T细胞的存在,移植物抗宿主病(GVHD)是HLA单倍型相同的HSCT的主要并发症,因此已采用不同方法在体外进行T细胞清除。最近已针对HLA单倍型相同的HSCT开发出清除供体αβT细胞(负责GVHD的亚群)和B细胞(负责移植后淋巴细胞增生性疾病)的方法。除了CD34祖细胞外,这种操作还保留了自然杀伤细胞、γδT细胞以及单核细胞/树突状细胞,有助于抗白血病活性并预防感染。我们分析了过去3年在我们中心进行的200例操作中的清除效率和细胞产量。供体通过粒细胞集落刺激因子(G-CSF)进行CD34造血干细胞(HSC)外周血动员。189例中48例(25%)CD34细胞动员效果不佳的供体除接受G-CSF外还接受了普乐沙福。使用CliniMACS设备对中位含有52.5×10有核细胞和494×10 CD34 HSC的单采物进行处理。与初始产物相比,αβT细胞清除导致中位减少4.1个对数(范围为3.1至5.5),B细胞清除导致中位减少3.4个对数(范围为2.0至4.7)。移植物产物中位含有18.5×10 CD34 HSC/kg受者体重,残余αβT细胞和B细胞的中位值分别为29×10/kg和33×10/kg。每6个月监测一次的清除效率显示性能稳定,而在第一年之后观察到CD34细胞的恢复有所改善(P = 0.0005)。这些数据表明,对来自HLA单倍型相同供体的HSC移植物进行αβT细胞和B细胞清除是有效且可重复的。