修正的供者淋巴细胞输注研究进展

造血干细胞移植(HSCT)已经成为恶性血液病的重要治疗手段.然而,移植后疾病复发可显著降低患者的长期生存率.修正的供者淋巴细胞输注(MDLI),输注的是经粒细胞集落刺激因子(G-CSF)动员的外周造血干细胞,而非静止状态的淋巴细胞.该方法能够减少供者淋巴细胞输注(DLI)后相关的移植物抗宿主病(GVHD)及复杂性血细胞减少,同时保留或者增强移植物抗肿瘤效应(GVT),因此MDLI已经广泛用于恶性血液病移植后复发的治疗.笔者拟就MDLI的作用机制、临床适应证、输注剂量、输注时机、间隔时间、疗效评估等进行综述.     

Influence of conditioning regimens and stem cell sources on donor-type chimerism early after stem cell transplantation

We retrospectively analyzed very early chimerism before and ongoing neutrophil engraftment (days 7, 14, 21, 28) and investigated the influence of conditioning regimens and stem cell sources on donor-type chimerism in 59 Japanese patients who had received allogeneic hematopoietic stem cell transplantation. The percentage of donor-type chimerism increased before engraftment in all patients who achieved engraftment. The average percentage of donor-type chimerism in patients who had received reduced-intensity stem cell transplantation (RIST) with total body irradiation (TBI) was significantly higher than that in patients who had received RIST without TBI (98.8% vs 87.5% on day 21, P < 0.01; 99.3% vs 84.3% on day 28, P < 0.01). The average percentage of donor-type chimerism after peripheral blood stem cell transplantation was significantly higher than that after bone marrow transplantation on day 7 (81.5% vs 43.1%, P < 0.01), and the average percentage of donor-type chimerism after cord blood transplantation was significantly lower on day 14 (55.8% vs 84.8%, P < 0.05). Compared with the average percentage of donor-type chimerism in patients who achieved engraftment with each stem cell source, a notable decrease in donor-type chimerism was observed in patients who failed to achieve engraftment. This study suggests that differences in conditioning regimens and stem cell sources should be taken into account when considering donor-type chimerism.     

游离缘指甲DNA检测异基因造血干细胞移植后供受者嵌合状态的变化

目的 探讨异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后用患者指甲游离缘标本进行短片段重复序列(short tandem repeat,STR)基因分型和供受者嵌合率检测的适用性,并观察移植后患者指甲中供受者嵌合状态变化.方法 选取2009年7月至2011年9月在北京市道培医院行allo-HSCT的25例患者及25名供者.采集患者及其供者外周血、骨髓、指甲游离缘和口腔黏膜标本.提取标本中基因组DNA,进行15个STR位点的基因分型和嵌合状态分析.将患者分为2组:第1组包括12例患者,在接受allo-HSCT后1个月内分别同时采集患者的指甲游离缘标本和口腔黏膜标本,并做嵌合状态的比较;第2组包括13例患者,观察患者行allo-HSCT后3个月指甲标本中的嵌合状态,并对其中3例患者进行多次指甲标本采集和嵌合状态检测.结果 在第1组12例患者中,指甲标本均检测为患者自身的STR基因型;在4份口腔黏膜标本中检测到供受者混合嵌合状态,供者STR基因型所占比例分别为16.7％、32.1％、35.8％和60.7％.在第2组13例患者中,5例患者存在供受者细胞的混合嵌合状态,即受者指甲中出现供者的STR基因型,嵌合率在6.7％至82.6％之间.3例行allo-HSCT后多次检测指甲嵌合率的患者中,1例始终未检测到供者基因型的嵌合,另2例患者中检测到持续存在的供者基因型的嵌合.结论 移植后1个月内采集的指甲游离缘标本可用于患者STR基因型鉴定和供受者嵌合率分析,优于口腔黏膜标本.供者的移植物中具有可以分化成为皮肤组织的细胞,部分患者移植后皮肤中可长期存在供者来源细胞的嵌合状态.