异基因骨髓移植和非清髓性干细胞移植嵌合形成过程的比较

Comparative study of chimerism dynamics between allogenic bone marrow transplantation and nonmyeloablative stem cell transplantation

目的研究异基因骨髓移植(allo-BMT)和非清髓性干细胞移植(NST)两种移植方式在供体细胞嵌合状态的形成及转归上的差异,探讨早期供体细胞植入的关键因素。方法对20例接受allo-BMT和18例NST的患者进行回顾性比较,研究两组患者疾病类型、干细胞来源、预处理方案和移植物抗宿主病预防方案。用复合扩增荧光标记STR-PCR结合毛细管电泳方法对移植后+7、+14、+21d,+1、+3、+6、+9、+12个月的嵌合体进行动态检测。结果(1)NST组在受体年龄、单个核细胞(MNC)、CD34+及T细胞数量上均明显高于BMT组,造血重建方面,中性粒细胞绝对值恢复时间与BMT组无差别,但血小板恢复明显早于BMT组。(2)NST组患者供体细胞完全嵌合状态(FDC)的建立比BMT组早(1个月vs3个月),移植后早期(+1个月)FDC比例亦明显高于BMT组(38·9%vs20%),而混合嵌合状态(MC)的发生率明显低于BMT组(61·2%vs80%),移植1个月后各时间段两组在嵌合体形成上均无显著性差别。(3)氟达拉滨为基础的NST预处理方案与标准预处理方案相比并未延迟供体细胞的植入。(4)NST组慢性移植物抗宿主病的发生率明显高于BMT组(80%vs50%,P<0·01),与NST组输入高剂量的CD34+细胞相关。结论在供体细胞早期植入和嵌合体形成的过程中,移植物中造血干细胞和T细胞数量至关重要,并可能起决定性作用。

Objective To explore whether the dynamics and outcome of chimerism are different between allogenic bone marrow transplantation（allo-BMT） and nonmyeloablative stem cell transplantation（NST） in order to define factors that significantly influence the earlyengraftment of donor stem cells. Methods A retrospective comparative study was performed between 20 patients undergoing BMT and 18 patients receiving NST. Sequential monitoring of chirnerism with 38 patients in different periods post transplantation using multiple short tandem repeat（STR） amplification by fluorescence labeling polymerase chain reaction（PCR） combined with a capillary electrophoresis. Results （1）The median age of recipient, median quantity of MNC, CD34^＋ cells and T lymphocyte cells of NST were significantly higher than those of BMT. The median time for absolute neutrophils recovery of NST （without G-CSF） was similar to that of BMT. While compared to BMT,NST led to faster engraftment of platelets. （2）The establishment of full donor chirnerism（FDC） of NST was much more earlier than that of BMT（1 month vs 3 months, P〈0.05）. In the early post-transplant period（up to day 30）, there was an apparent increase in the incidence of full donor chimerism（FDC） following NST compared with that following BMT（38. 9% vs 20%,P〈0. 05）. Whereas a significantly lower incidence of mixed chi- merism（MC） occurred in recipients of NST compared to that of BMT（61.2% vs 80% ,P〈0.05）. The major relevant factor causing full donor chimerism formation seemed to be the high quantity of donor CD34^＋ cells and T lymphocyte cells. （3）Fludarahine-hased reduced-intensity conditioning did not result in a significant delay of donor cell engraftment compared to standard conditioning regimen. （4） The incidence of chronic GVHD was much higher in group of NST than that in BMT group（80% vs 50% ,P〈0. 01）. This finding was related to that patients of NST group received the higher doses of CD34^＋ cells. Conclusion The key factor that significantly influences the early kinetics of donor chimerism and donor cell engraftment after transplantation is the quantity of stem cell and T lymphocyte cell of grafts.