Low efficiency of a newly introduced high-density microparticles method for B cell depletion in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.

P Perseghin, M Dassi, D Belotti, P Pioltelli, E M Pogliani
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引用次数: 1

Abstract

Autologous peripheral blood stem cell (PBSC) transplantation proved to increase complete remission (CR) and DFS in multiple myeloma (MM) patients. CD34(+) cell selection has been used to reduce possible myeloma cell contamination in the graft, but it has not been showed to offer substantial advantages when compared to unpurged grafts; on the contrary, an increase of infectious complications was observed. We investigated the feasibility of a new negative-selection method in this setting. B cell negative selection was performed by using Eligix B cell HDM method. B cell contamination in the yield and in the final product was investigated by flow cytometry. Three patients with newly diagnosed MM entered the study. CD34(+) cell recovery in the three procedures was 73, 97, and 106%, and CD3(+) cell recovery was 88, 86, and 102%, respectively. CD20(+) cell depletion was 100% in all procedures, while CD19(+) cell depletion was 0.37, 1.21, and 0.07 log, respectively. We found an unexpected unreliability and a low efficiency in this B cell depletion method and suggest the need for further extensive testing before its introduction in the preclinical and clinical settings, at least in MM patients. In fact, reasons of such unsatisfactory results are still controversial: platelet contamination/activation in the preselection product, plasma protein interference, reduced CD19 antigen expression on immature B cells, lack of specificity of anti-CD19 monoclonal antibodies, instable binding between anti-CD19-coated high-density microparticles (HDM) and CD19 antigen may, alone or in combination, be involved in the system's low performance.

在自体造血干细胞移植的多发性骨髓瘤患者中,一种新引入的高密度微粒法对B细胞的清除效率低。
自体外周血干细胞(PBSC)移植可增加多发性骨髓瘤(MM)患者的完全缓解(CR)和DFS。CD34(+)细胞选择已被用于减少移植物中可能的骨髓瘤细胞污染,但与未清除的移植物相比,它尚未显示出实质性的优势;相反,观察到感染并发症的增加。我们研究了一种新的负选择方法在这种情况下的可行性。采用Eligix B细胞HDM法进行B细胞阴性选择。用流式细胞术检测产率和终产物中的B细胞污染情况。3例新诊断的MM患者进入研究。三种方法的CD34(+)细胞回收率分别为73,97和106%,CD3(+)细胞回收率分别为88,86和102%。CD20(+)细胞损耗在所有程序中为100%,而CD19(+)细胞损耗分别为0.37,1.21和0.07 log。我们发现这种B细胞消耗方法存在意想不到的不可靠性和低效率,并建议在将其引入临床前和临床环境之前,至少在MM患者中,需要进一步进行广泛的测试。事实上,造成这种不理想结果的原因仍然存在争议:预选产物中的血小板污染/活化、血浆蛋白干扰、未成熟B细胞上CD19抗原表达降低、抗CD19单克隆抗体缺乏特异性、抗CD19包被高密度微粒(HDM)与CD19抗原结合不稳定等可能单独或联合导致系统性能低下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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