【摘要】：目的:白血病患者完全緩解后復(fù)發(fā)最主要的根源是骨髓中微小殘留病的持續(xù)存在。國(guó)內(nèi)外學(xué)者大多數(shù)選擇化療后某個(gè)時(shí)間點(diǎn)檢測(cè)MRD,較少對(duì)MRD在化療過(guò)程中的變化趨勢(shì)進(jìn)行研究。本研究目的在于動(dòng)態(tài)監(jiān)測(cè)CR后和鞏固化療后多個(gè)時(shí)間點(diǎn)微小殘留病與復(fù)發(fā)的關(guān)系。進(jìn)一步探討微小殘留病在監(jiān)測(cè)病程的發(fā)展、臨床療效評(píng)估、判斷預(yù)后中的價(jià)值。方法:回顧性分析青島大學(xué)附屬醫(yī)院2012年9月至2016年12月收治的急性髓細(xì)胞白血病(AML)患者(51例),其中男30例(58.8%),女21例(41.2%),中位年齡40歲(14~66歲),其中M1 1例(2%),M2 9例(18%),M3 11例(21%),M4 18例(35%),M5 12例(24%)。對(duì)51例急性髓系白血病完全緩解患者平均每3個(gè)月(1-6個(gè)月)用FCM檢測(cè)其骨髓MRD,同時(shí)檢測(cè)骨髓細(xì)胞形態(tài)學(xué)的變化。隨訪至形態(tài)學(xué)復(fù)發(fā)或隨訪終止,平均跟蹤隨訪12個(gè)月,得出完全緩解病人的MRD平均值,分析其變化趨勢(shì)。同時(shí)監(jiān)測(cè)CR后和鞏固化療1個(gè)療程和2個(gè)療程后3個(gè)不同時(shí)間點(diǎn)微小殘留與復(fù)發(fā)的關(guān)系。根據(jù)AML患者經(jīng)誘導(dǎo)治療達(dá)CR時(shí)的MRD值分為:MRD≤10-4、10-4MRD10-3、10-3≤MRD≤10-2、MRD10-2 4組,評(píng)估不同時(shí)間點(diǎn)MRD水平在AML患者預(yù)后中的價(jià)值。MRD10-4為微小殘留病陽(yáng)性標(biāo)準(zhǔn)。結(jié)果:51例AML患者經(jīng)化療達(dá)到CR后測(cè)得MRD最大值4.97%,最小值0.0062%,平均值0.57%;鞏固治療1療程后測(cè)得MRD最大值4.72%,最小值0.0053%,平均值0.38%,其中47例AML患者CR后MRD檢測(cè)呈陽(yáng)性(10-4)結(jié)果,4例AML患者CR后MRD檢測(cè)出陰性(10-4)的結(jié)果。鞏固治療2療程后測(cè)得MRD最大值3.11%,最小值0.0037%,平均值0.21%;鞏固化療第2個(gè)療程后MRD陽(yáng)性患者中有5例患者M(jìn)RD由陽(yáng)性轉(zhuǎn)為陰性,1例由陰性轉(zhuǎn)為陽(yáng)性。選擇不同時(shí)間點(diǎn)平均隨訪12個(gè)月(0-24個(gè)月)后獲得骨髓形態(tài)學(xué)復(fù)發(fā)例數(shù):MRD"f10-4組復(fù)發(fā)1例,復(fù)發(fā)率1.96%;10-4MRD10-3組復(fù)發(fā)4例,復(fù)發(fā)率7.84%;10-3"fMRD"f10-2組復(fù)發(fā)8例,復(fù)發(fā)率15.69%;MRD10-2組復(fù)發(fā)14例,復(fù)發(fā)率27.45%。用Kaplan-Meier法分析四組的無(wú)復(fù)發(fā)生存期,差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05)。MRD"f10-4組,10-4MRD10-3組,10-3"fMRD"f10-2組,MRD10-2組,平均中位無(wú)復(fù)發(fā)生存時(shí)間(RFS)分別為23.1個(gè)月、14.3個(gè)月、9.1個(gè)月、3.5個(gè)月。結(jié)論:1.MRD是治療過(guò)程中監(jiān)測(cè)急性髓系白血病緩解與復(fù)發(fā)的重要指標(biāo)之一,以FCM動(dòng)態(tài)監(jiān)測(cè)AML CR后的MRD變化情況,可為個(gè)體化治療及預(yù)后提供臨床依據(jù)。2.FCM動(dòng)態(tài)監(jiān)測(cè)急性髓系白血病CR后MRD的差異較大,不能作為評(píng)價(jià)臨床預(yù)后的單一指標(biāo)。3.通過(guò)上述臨床研究結(jié)果分析,MRD可以作為預(yù)后評(píng)價(jià)的敏感指標(biāo)。MRD小于10-4復(fù)發(fā)可能性小,大于10-4提示疾病復(fù)發(fā)可能性大,且MRD值越小無(wú)復(fù)發(fā)生存期越長(zhǎng)。隨著鞏固化療次數(shù)的增加、治療時(shí)間的延長(zhǎng),骨毮MRD水平總體上呈下降趨勢(shì)。
[Abstract]:Objective: the primary cause of relapse after complete remission in leukemia patients is the persistence of minimal residual disease in bone marrow. Most scholars at home and abroad choose to detect MRD, at some time point after chemotherapy, and seldom study the change trend of MRD in the course of chemotherapy. The aim of this study was to dynamically monitor the relationship between minimal residual disease and recurrence at multiple time points after CR and consolidation chemotherapy. To further explore the value of minimal residual disease in monitoring the development of disease course, evaluation of clinical efficacy and judgment of prognosis. Methods: a retrospective analysis of 51 patients with acute myeloid leukemia (AML) admitted from September 2012 to December 2016 in the affiliated Hospital of Qingdao University, including 30 males (58.8%) and 21 females (41.2%), with a median age of 40 (1466 years), including 1 case (2%) of M1, 9 cases (18%) of M 2, M3 11 cases (21%), M 4 18 cases (35%), M 5 12 cases (24%). The bone marrow MRD, of 51 patients with complete remission of acute myeloid leukemia was detected by FCM every three months (1-6 months) and the morphologic changes of bone marrow cells were also detected. The mean value of MRD in patients with complete remission was obtained and the trend of change was analyzed. At the same time, the relationship between minimal residual and recurrence at 3 different time points after CR, one course of consolidation chemotherapy and two courses of treatment were monitored. According to the MRD value of AML patients after induction treatment to CR, they were divided into four groups: MRD 鈮，

本文編號(hào)：2268266