异基因造血干细胞移植适应证及疗效

异基因造血干细胞移植(allogeneic hematopoietic stem cell transplant,Allo-HSCT)是治疗造血系统疾病有效的方法.根据国际骨髓移植登记处(international bone marrow transplant registry,IBMTR)的统计,从1970～2004年,在IBMTR登记的Allo-HSCT病例数已接近5万例,而且每年以近3 000例的数量增加;而IBMTR并不包括全世界所有完成的Allo-HSCT病例.我国自上世纪80年代后期由少数几家移植中心开始Allo-HSCT工作到目前除西藏以外所有省、市、自治区均可开展Allo-HSCT工作;在不少地区,该项技术向县、市级医疗机构延伸;随着完成的病例数逐渐增加,远期疗效也逐渐提高.

异基因造血干细胞移植后早期特发性肺炎综合征的相关危险因素分析

大剂量化疗后行异基因造血干细胞移植(allo-HSCT)已成为治疗血液系统恶性肿瘤的有效手段.40%～60%的患者在allo-HSCT后出现肺部并发症,其中10%～40%的患者因肺部并发症而死亡,成为影响移植预后的一个重要因素[1].特发性肺炎综合征(IPS)是allo-HSCT后常见的肺部并发症,发生率在3%～15%,但其病死率高达60%以上.IPS的病因不清楚,目前倾向于IPS的发生可能与移植前放射预处理及合并急性移植物抗宿主病(GVHD)等有关[2-3].我们以我院近年接受allo-HSCT的患者为研究对象,分析alloHSCT患者中IPS的发病率及相关危险因素.

Background:Hematopoietic stem cell (HSC) transplantation can be used to treat blood and immune system disorders. Fresh umbilical cord blood (UCB), a major source of HSC for potential clinical applications, contains a limited number of HSCs. Stem cell factor (SCF) activates HSC self-renewal and is being used to stimulate ex vivo expansion of HSCs for treating various hematologic diseases in clinic. Yet, the mechanism by which SCF stimulates and supports HSCs expansion remains poorly understood. Thus, the purpose of the study is to obtain novel monoclonal antibodies for structural and functional SCF characterizations, as well as for the optimization of HSCs ex vivo expansion. Methods:Recombinant human stem cell factor (rhSCF) was used for producing monoclonal antibody (mAb). High-titer mAb speciifc to rhSCF was selected by following immunochemical screening to various mAb cell lines. HSCs with CD34+ epitope were isolated from UCB using affinity chromatography. SCF activity was tested in an ex vivo HSC expansion assay, with use of flow cytometry for detection of CD34+ cell and total mononuclear cells. Part of rhSCF that contained the antibody-binding site was identified via immunoblot analysis of rhSCF tryptic peptides, rhSCF-speciifc mAb, and subsequent NH2-terminal amino acid sequence analysis of the detected peptides. Results: The mAb cell line 23C8 with a high titer was found to be speciifc for rhSCF. In ex vivo cord blood expansion assays, the ability of rhSCF to stimulate the expansion of CD34+ cells was significantly inhibited by 23C8 in a dose-dependet fashion(?). Through peptide mapping, the binding site of 23C8 on rhSCF was mapped to the ifrst 104 amino acids.. Conclusion: The mAb cell line 23C8 produces speciifc and inhibitory anti-rhSCF mAb. The mAb appears to bind directly to a part of rhSCF that is critical for biological activity. This functionally active site of rhSCF is located in the ifrst 104 amino acids from the NH2-terminus. The novel anti-rhSCF mAb will be valuable for further dissection of SCF functional domains and optimization of HSCs ex vivo expansion.