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目的探究供体细胞嵌合率(DC)的动态定量检测在预测异基因造血干细胞移植(alloHSCT)后的转归,确定过继免疫治疗(AIT)时机和评价AIT疗效中的作用。方法采用复合扩增荧光标记短串联重复片段(STR)PCR结合毛细管电泳方法,对84例alloHSCT患者骨髓或外周血中DC进行定量检测,并对其中接受AIT的16例患者治疗前后的DC进行连续定量检测。结果移植后84例患者中有22例出现受体细胞比例增高的混合嵌合(MC)状态,DC均低于90%,6例MC患者未接受供体淋巴细胞输注(DLI)治疗,结果均死于血液学复发,另外16例患者接受AIT治疗,其中复发和植入失败的12例患者在出现临床症状之前DC均出现大幅度下降(24.8%～86.2%)。16例中11例出现治疗反应(有效率68.8%)。治疗有效患者在AIT后短期内出现DC回升(DC≥90%),供体细胞占优势,并转化为完全供体细胞嵌合状态(6/11)或稳定的MC状态(5/11),临床上出现移植物抗宿主病表现。无效患者AIT后DC均未稳定回升,3例首次DLI无效的患者接受了第二次DLI治疗。结论DC的动态定量检测可早期发现复发或植入失败的高危患者,尽早实施AIT,可提高发生细胞遗传学或分子生物学复发患者的疗效。此外DC的定量检测还可预测DLI的临床疗效,对首次DLI治疗无效的患者后继的AIT提供重要的参考依据。
Objective To investigate the dynamic quantitative detection of donor chimerism (DC) in the prognosis of alloHSCT, determine the timing of adoptive immunotherapy (AIT) and evaluate the effect of AIT. Methods A total of 84 cases of alloHSCT patients with bone marrow or peripheral blood were quantitatively detected by multiplex amplification of fluorescent labeled short tandem repeat (STR) PCR and capillary electrophoresis. The DCs in 16 patients with AIT before and after treatment were continuously Quantitative detection. Results Twenty-two of the 84 patients showed mixed MC status, the DCs were lower than 90%, and 6 MC patients were not treated with DLI. All died of hematologic relapse. Another 16 patients underwent AIT. Among them, 12 patients who relapsed and failed to implant had a significant decrease in DC before onset of clinical symptoms (24.8% -86.2%). In 16 cases, 11 patients showed response to therapy (effective rate 68.8%). After treatment with AIT, DCs rose rapidly (DC≥90%) in donor-treated patients, predominantly donor cells, and converted to complete donor cell chimerism (6/11) or stable MC status (5/11) Clinical manifestations of graft versus host disease. DCs in patients with ineffective disease did not rise steadily after AIT, and 3 patients with first-episode DLI were ineligible for the second DLI. Conclusions The dynamic quantitative detection of DC can early identify patients at high risk of recurrent or failed implantation. As soon as possible, AIT may improve the efficacy of DC in patients with recurrent cytogenetics or molecular biology. In addition, the quantitative detection of DC can predict the clinical efficacy of DLI, providing an important reference for the subsequent AIT of patients with no first DLI treatment.