异基因造血干细胞移植后CD4^(+)和CD8^(+)T细胞ATP水平的临床意义

Clinical utility of CD4 and CD8 T-lymphocytes ATP levels in patients following allogeneic hematopoietic stem cell transplantation

目的:探讨荧光素酶法检测CD4^(+)和CD8^(+)T淋巴细胞三磷酸腺苷(ATP)水平在异基因造血干细胞移植(allo-HSCT)后感染、急性移植物抗宿主病(aGVHD)及疾病复发的变化和临床意义。方法:纳入2019年1月—2020年5月接受allo-HSCT的血液系统肿瘤患者为研究对象,荧光素酶法检测allo-HSCT后不同时间点患者的CD4^(+)和CD8^(+)T细胞ATP水平,分析其与aGVHD、感染和肿瘤复发的关系。结果:纳入本研究患者26例,中位年龄31(17~64)岁。allo-HSCT后ATP^(CD4)和ATP^(CD8)分别为(217.50±117.59)ng/mL和(196.23±117.32)ng/mL,均比健康人群低(P<0.05)。发生aGVHD的中位时间为+48(+25~+184)d,发生Ⅲ~Ⅳ度aGVHD患者基础ATP^(CD4)比轻度和未发生GVHD的患者明显下降(P=0.018),而且,aGVHD时的ATP^(CD4)比粒细胞重建时更低,aGVHD缓解后ATP^(CD4)和ATP^(CD8)均比起病时明显回升(P<0.01)。allo-HSCT后感染的中位时间为+67(+36~+218)d。感染后平均ATP^(CD4)比感染前明显下降(P=0.047),基础ATP水平在+67 d内感染和非感染患者间差异无统计学意义。总体中位随访时间为31(3~39)个月,2年内复发患者8例(30.77%),死亡患者8例(30.77%)。复发患者基础ATP^(CD4)比无复发患者明显下降(P=0.009),基础ATP^(CD4)≤99.90 ng/mL是死亡的独立危险因素(P=0.009)。结论:ATP^(CD4)对预测Ⅲ~Ⅳ度严重GVHD和疾病复发及不良预后有一定价值。

Objective:To evaluate the clinical utility of CD4 and CD8 T-lymphocytes adenosine triphosphate(ATP)levels in predicting infection,acute GVHD(aGVHD)and disease relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Patients with hematology malignancy who underwent allo-HSCT between January 2019 to May 2020 were retrospectively studied.Luminescent ATP detection assay was used to assess CD4 and CD8 ATP levels which were compared at different time points when patients had neutrophil reconstitution,aGVHD onset,infection and disease relapse.Results:A total of 26 patients were included with the median age of 31 years(range 17-64 years).CD4 and CD8 ATP levels at the time of neutrophil reconstitution were(217.50±117.59)ng/mL and(196.23±117.32)ng/mL,respectively,which were much lower than those of healthy people(P<0.05).Patients developed aGVHD at a median time of+48 d(range+25 to+184 days).Initial CD4 ATP levels of patients with gradeⅢ-ⅣaGVHD were significantly lower than those with gradeⅠ-Ⅱor without aGVHD(P=0.018).CD4 ATP levels during aGVHD were lower than initial levels but increased as aGVHD improved(P<0.01).Patients had infection at a median time of+67 d(range+36 to+218 days).CD4 ATP levels during infection were lower than initial levels which showed no difference between patients with or without infection within+67 d post allo-HSCT.Patients were followed up for 3 to 39 months with a median follow-up of 31 months and 8 patients(30.77%)relapsed and 8 patients(30.77%)died within 2 years.CD4 ATP levels at relapse was dramatically decreased and initial CD4 ATP levels of≤99.90 ng/mL was confirmed to be a risk factor for poor clinical outcome(P=0.009).Conclusion:Assessment of CD4 and CD8 ATP levels by Luminescent ATP Detection Assay Kit play an important role in predicting gradeⅢ-ⅣaGVHD and disease relapse after allo-HSCT.