Tabilio Antonio, Falzetti Franca, Zei Tiziana, De Ioanni Maria, Bonifacio Elisabetta, Battelli Feliciana, Iacucci Ostini Roberta, Ballanti Stelvio, Cimminiello Michele, Capponi Monia, Silvani Carla, Minelli Olivia, Fettucciari Katia, Marconi Pierfrancesco, Rosati Emanuela, Santucci Antonella, Di Ianni Mauro, Aversa Franco, Martelli Massimo F
Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology, University of Perugia, Perugia, Italy.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):274-80. doi: 10.1016/j.bcmd.2004.08.016.
Haploidentical stem cell transplantation has became a clinical reality in the last 10 years as it provides the chance of transplant for about 50% of patients with hematological malignancies who do not have a matched related or unrelated donor. Proper graft preparation for this type of transplant is crucial and this paper analyses our work over the past decade in the search for the optimal graft processing procedure moving from E-rosetting and soybean agglutination, through a combination of negative or positive selection of hematopoietic stem cells to the current method of one-step positive selection. In preparing a graft for haploidentical transplant, three essential requisites must be met. It must contain (1) a megadose (>10 x 10(6) x kg recipient b.w.) of hematopoietic stem cells to overcome the HLA histocompatibility barrier; (2) very few T-lymphocytes (CD3+ cells < 3 x 10(4)/kg recipient b.w.) to prevent severe acute and chronic graft-versus-host disease (GvHD); (3) very few B-lymphocytes to prevent Epstein-Barr virus-related lymphoproliferative disorders. With current graft processing technologies based on positive selection of hematopoietic stem cells, these requirements can be met. A 70-80% hematopoietic stem cell recovery ensures the target megadose is achieved in over 70% of cases with a T-cell depletion of more than 4 logs and a B-cell depletion of over 3 logs. Progress in graft processing has ensured primary, sustained engraftment rates of over 90% and has significantly reduced the incidence of severe acute GvHD and EBV-related lymphoproliferative disorders. Modern time-saving automated graft processing devices ensure reproducibility, reliability, and biological safety, which make widespread application of the haploidentical transplant currently feasible.
在过去十年中，单倍体相合干细胞移植已成为临床现实，因为它为约50%没有匹配的相关或无关供体的血液系统恶性肿瘤患者提供了移植机会。为这类移植进行适当的移植物制备至关重要，本文分析了我们在过去十年中的工作，以寻找最佳的移植物处理程序，从E花环沉降法和大豆凝集法，经过造血干细胞的阴性或阳性选择组合，到目前的一步阳性选择法。在制备单倍体相合移植的移植物时，必须满足三个基本要求。它必须包含：(1) 大剂量（>10×10⁶×kg受者体重）的造血干细胞，以克服HLA组织相容性屏障；(2) 极少的T淋巴细胞（CD3⁺细胞<3×10⁴/kg受者体重），以预防严重的急性和慢性移植物抗宿主病（GvHD）；(3) 极少的B淋巴细胞，以预防与EB病毒相关的淋巴增殖性疾病。采用基于造血干细胞阳性选择的当前移植物处理技术，可以满足这些要求。70%-80%的造血干细胞回收率可确保在超过70%的病例中达到目标大剂量，T细胞清除率超过4个对数，B细胞清除率超过3个对数。移植物处理方面的进展确保了超过90%的初次、持续植入率，并显著降低了严重急性GvHD和EBV相关淋巴增殖性疾病的发生率。现代节省时间的自动化移植物处理设备确保了可重复性、可靠性和生物安全性，这使得单倍体相合移植目前得以广泛应用。
