非血缘异基因脐血造血干细胞移植现状、问题与对策

Unrelated Allogeneic Umbilical Cord Blood Transplantation:Present Status,Problems and Countermeasures

非血缘异基因脐血移植(UCBT)自1988年第一例发展至今已经经历了20年。全世界报道脐血移植的病例已经累积10 000例以上。大量的临床研究报告和统计学处理结果已有力地证实非血缘异基因脐血移植是有显效的,HLA0-1位点不合的UCBT的临床TRM、复发率和无复发生存率等数据和HLA全相合骨髓移植的相仿,但UCBT的重度GVHD发生率明显减少。已经公认:异基因脐血无疑是一个造血干细胞随时可取到的新来源,尤其当病人不能及时找到合适的HLA全相合非血缘骨髓供者,也没有单倍体相合的外周血供者时。近年来,异基因脐血移植的两大新发展,一是脐血双份移植,一是脐血移植用于非恶性的难治性疾病治疗(如重症免疫缺损、地中海贫血、骨髓衰竭综合症和代谢障碍病等等)。脐血双份移植用于大体重儿童或成人病例并获得成功报告越来越多,其发展势头超过了儿童单份UCBT病例。双份异基因脐血移植的临床成功实践给有关基础研究提出许多令人困惑而又饶有兴趣的问题,例如HLA互不相合的双份脐血在体内的'斗争'究竟是什么,为什么不破坏整个移植,反而提高了植入率?双份脐血有核细胞剂量之和并不高于单份脐血移植成功的剂量,而每单份的细胞剂量都低于单份脐血移植成功需要的剂量,这样反而提高了植入率,为什么?双份脐血之间,受者之间的HLA都互不相合,为什么受者可以在第一阶段容纳双份脐血同时植入,以后双份脐血中只有一份可长期植入,又为什么?那一份脐血细胞能优胜而长期植入的因素是什么?本文参考国际UCBT文献,就如何评价非血缘性异基因UCBT存在的问题,采取对策及其发展前景,加以讨论。

As unrelated allogeneic umbilical cord blood transplantation （UCBT） has been developed for 20 years already since 1988, more than ten thousands cases have cumulatively undergone UCBT over the world. A huge number of clinical data confirmed that UCBT had unique characters with low rate of severe GVHD. The efficacy and data on TRM, relapse and EFS of allogeneic UCBT with HLA 0 - 1 mismatched are similar to those in HLA matched BMT. UCBT has become the optimal choice for source of hematopoietic stem cells for allogeneic stem cell transplant especially when HLA-matched or haploidentical donors are not available in time. In most developed countries, unrelated allogeneic UCBT developed successively, and in recent years HLA mismatched UCBT with double units performed in adults increased even more rapidly than in children. Another recent trend of UCBT has been extending to treat some non- malignant but refractory diseases in pediatrics, such as severe combined immunodeficiency, thalassemia major, bone marrow failure syndrome and metabolic disorders. The clinical successful practice of double units for cord blood transplantation inspires to ponder over questions remaining mystery. What is the conflict like between two mismatched donor cells in vivo, which does not spoil the whole transplantation but enable the patient to be engrafted successfully without any increment of the dosage by the sum of two doses together？ How can they both be taken at the same time firstly by the recipient, but why does only one predominate later？ What are the factors enable the donor cells of the winner to sustain？ With the references of the international experiences, how to solve the clinical encountered problems, perspective of unrelated allogeneic UCBT and proper strategies to be enacted are reviewed.