Detection of minimal residual disease prior to allogeneic hematopoietic cell transplantation in middle-aged and elderly acute myeloid leukemia patients: a meta-analysis

doi:10.3969/j.issn.2095-4344.0628

Abstract

Abstract:

BACKGROUND: Residual leukemia cells still remain in the body of leukemia patients who are in complete remission at clinical and blood cytology levels. Therefore, minimal residual disease (MRD) is considered to be highly correlated with leukemia recurrence. Whether the MRD status affects the survival of patients after allogeneic hematopoietic stem cell transplantation remains the focus of controversy.
OBJECTIVE: To evaluate the prognostic role of minimal residual disease (MRD) testing before allogeneic hematopoietic stem cell transplantation.
METHODS: Published literature regarding MRD testing in middle-aged and elderly acute myeloid leukemia patients before allogeneic hematopoietic stem cell transplantation within CNKI, VIP Database, WanFang Database, PubMed, Embase, and the Cochrane Library were searched in this meta-analysis. Data were analyzed with the Stata 12.0 software package using pooled hazard ratios (HR) with 95% confidence intervals (CI).
RESULTS AND CONCLUSION: A total of 8 studies involving 908 patients (227 positive for MRD and 681 negative for MRD) were included. The results of meta-analysis showed that pre-transplant MRD was associated with poor overall survival (HR=11.81, 95%CI: 4.76-29.31, P=0.000 1), disease-free survival (HR=10.75, 95%CI: 3.73-30.96, P=0.0001), cumulative incidence of relapse (HR=44.15, 95%CI: 13.20-147.69, P=0.000 1), and non-relapse mortality (HR=2.14, 95%CI: 1.48-3.10, P=0.001). To conclude, pre-transplant MRD (positive for MRD) may indicate poor prognosis in middle-aged and elderly acute myeloid leukemia patients. Therefore, a rational method to screen MRD is necessary prior to allogeneic hematopoietic stem cell transplantation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Leukemia, Hematopoietic Stem Cell Transplantation, Aged, Middle Aged, Stem Cells

CLC Number:

R394.2

Feng You-fan, Wei Xiao-fang, Zhang Qi-ke. Detection of minimal residual disease prior to allogeneic hematopoietic cell transplantation in middle-aged and elderly acute myeloid leukemia patients: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(29): 4692-4697.

Figures/Tables 5

2.2 总生存期的Meta分析纳入的8项研究均报告了患者的总生存期资料[7-14]，异质性检验结果显示I2=74.2%，P=0.000 1，提示研究间存在统计学异质性，故采用随机效应模型进行Meta分析。数据合并结果显示：异基因造血干细胞移植术前MRD阳性与阴性患者之间总生存期的差异有统计学意义(HR=11.81，95%CI：4.76-29.31，P=0.000 1)，见图2。 2.3 无疾病进展期的Meta分析纳入的研究中7项报告了患者的无疾病进展期资料[7-9，11-14]，异质性检验结果显示I2=73.8%，P=0.001，提示研究间存在统计学异质性，故采用随机效应模型进行Meta分析。数据合并结果显示：异基因造血干细胞移植术前MRD阳性与阴性患者之间无疾病进展期的差异有统计学意义(HR=10.75，95%CI：3.73-30.96，P=0.000 1)，见图3。 2.4 累积复发率的Meta分析纳入的研究中7项报告了患者的累积复发率[7-10，12-14]，异质性检验结果显示I2=0.0%，P=0.667，提示研究间统计学异质性较小，故采用固定效应模型进行Meta分析。数据合并结果显示：异基因造血干细胞移植术前MRD阳性与阴性患者之间累积复发率的差异有统计学意义(HR=44.15，95%CI：13.20-147.69，P=0.000 1)，见图4。 2.5 非复发死亡率的Meta分析纳入的研究中7项报告了患者的非复发死亡率[7-10，12-14]，异质性检验结果显示I2=13.1%，P=0.330，提示研究间统计学异质性较小，故采用固定效应模型进行Meta分析。数据合并结果显示：异基因造血干细胞移植术前MRD阳性与阴性患者之间非复发死亡率的差异有统计学意义(HR=2.14，95%CI：1.48-3.10，P=0.001)，见图5。 2.6 发表偏倚风险评估绘制漏斗图发现，纳入的研究具有向漏斗顶部集中的趋势，提示阴性结果未被发表的可能性较小，如图6。"

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