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[异基因造血干细胞移植后急性白血病患者微小残留病的流式细胞术监测]

[Flow cytometric monitoring of minimal residual diseases in patients with acute leukemia after allogeneic hemapoietic stem cell transplantation].

作者信息

Gao Yan-Qun, Wu Tong, Wang Hui, Tong Chun-Rong, Zhang Wei-Jie, Wang Jing-Bo, Lu Yue, Zhao Yan-Li, Zhou Jia-Rui, Sun Yuan, Zhang Yao-Chen, Ji Shu-Quan, Lu Dao-Pei

机构信息

Beijing Daopei Hospital 100049, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2012 Feb;33(2):84-7.

PMID:22730653
Abstract

OBJECTIVE

To study the significance of flow cytometric monitoring minimal residual diseases (MRD) in patients with acute leukemia (AL) after allogeneic hemapoietic stem cell transplantation (HSCT).

METHODS

From January 2007 and January 2008 MRD were detected by flow cytometry (FCM) in 402 bone marrow (BM) in 102 AL patients without leukemic gene and chromosomal changes at first diagnosis after HSCT (1, 2, 3, 6,12 months after HSCT; adding detection frequency in part of high risk patients), The relationship between the MRD results and clinical prognosis were observed. Patients with significantly higher MRD were treated and the effectiveness was monitored by FCM (MRD > 0.01% considered as positive).

RESULTS

(1) 71 cases were persistently negative for MRD after HSCT and all them were in hematologic complete remission (CR). Only 3 cases had extramedullary relapse. The disease free survival (DFS) and overall survival (OS) were 66.2% and 90.1%, respectively. (2) Of 27 MRD(+) cases 11 converted to MRD negativity after chemotherapy plus donor lymphocyte infusion (DLI), CIK, NK cells. The DFS and OS were 63.6% and 72.7%, respectively. Other 16 cases had hematologic relapse. The DFS and OS were 11.1% and 25.0%, respectively. The median time from MRD increasing to hematologic relapse was 48 days (7-69 day). (3) Four cases had hematologic relapse after HSCT and died in the end.

CONCLUSIONS

(1) The DFS and the OS in MRD(-) cases are significantly higher than those of MRD(+) cases. (2)MRD(+) patients after HSCT coveted to MRD(-) after intervention. Therapy, whose DFS and the OS are still significantly higher than those of MRD(+) cases. (3) Patients with hematologic relapse after HSCT have the worst prognosis and the DFS and OS are significantly low. FCM monitoring of MRD in patients after HSCT is a sensitive, specific, quick and simple method. It can indicate recurrent state in time, facilitates early intervention, reduces the hematologic relapse risk and improves DFS.

摘要

目的

探讨流式细胞术监测异基因造血干细胞移植(HSCT)后急性白血病(AL)患者微小残留病(MRD)的意义。

方法

2007年1月至2008年1月,采用流式细胞术(FCM)检测102例初诊时无白血病基因及染色体改变的AL患者HSCT后(HSCT后1、2、3、6、12个月;部分高危患者增加检测频率)402份骨髓(BM)中的MRD,观察MRD结果与临床预后的关系。对MRD明显升高的患者进行治疗,并通过FCM监测疗效(MRD>0.01%视为阳性)。

结果

(1)71例患者HSCT后MRD持续阴性,均处于血液学完全缓解(CR)状态。仅3例发生髓外复发。无病生存率(DFS)和总生存率(OS)分别为66.2%和90.1%。(2)27例MRD(+)患者中,11例经化疗加供者淋巴细胞输注(DLI)、CIK、NK细胞治疗后转为MRD阴性。DFS和OS分别为63.6%和72.7%。其余16例发生血液学复发。DFS和OS分别为11.1%和25.0%。从MRD升高到血液学复发的中位时间为48天(7 - 69天)。(3)4例患者HSCT后发生血液学复发,最终死亡。

结论

(1)MRD(-)患者的DFS和OS显著高于MRD(+)患者。(2)HSCT后MRD(+)患者经干预后转为MRD(-)。其DFS和OS仍显著高于MRD(+)患者。(3)HSCT后发生血液学复发的患者预后最差,DFS和OS显著降低。FCM监测HSCT后患者的MRD是一种敏感、特异、快速且简便的方法。它能及时提示复发状态,便于早期干预,降低血液学复发风险,提高DFS。

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