本文選題：多發(fā)性骨髓瘤 + 常規(guī)細胞遺傳學�。� 參考：《河北醫(yī)科大學》2017年碩士論文

【摘要】：目的:應用熒光原位雜交(flurorescence in situ hybridization,FISH)技術檢測多發(fā)性骨髓瘤(multiple myeloma,MM)患者染色體異常的發(fā)生情況及其與MM患者性別、年齡、分期、血常規(guī)、生化等臨床資料、療效及預后的關系,明確疾病預后危險分層,探討其臨床意義。方法:收集河北醫(yī)科大學第三醫(yī)院血液科自2013年2月1日至2017年1月1日初診的66例MM患者骨髓標本,進行CD138磁珠分選富集漿細胞后,利用FISH技術,采用特異性探針(包括1q21、TP53、D13S319、IGH/CCND1、IGH/FGFR3、IGH/MAF探針)檢測66例MM患者染色體異常的發(fā)生情況。結(jié)果:1 FISH結(jié)果1.1染色體異常的檢出率:在66例MM患者中55例出現(xiàn)染色體異常,總異常檢出率為83.3%(55/66)。累及探針個數(shù)≥2個占56.1%(37/66),用TP53探針檢測17號染色體缺失,陽性率為12.1%(8/66);IGH探針檢測14號染色體異常,陽性率為54.5%(36/66):其中IGH/MAF陽性率為3.0%(2/66),IGH/FGFR3陽性率為13.6%(9/66),IGH/CCND1陽性率為25.8%(17/66);用D13S319探針檢測13號染色體缺失,D13S319陽性率為40.9%(27/66);用1q21探針檢測1號染色體異常,1q21擴增陽性率為47.0%(31/66)。1.2 D13S319與IGH之間的關系:D13S319與IGH/FGFR3卡方檢驗發(fā)現(xiàn)D13S319陽性患者常伴隨IGH/FGFR3陽性,具有統(tǒng)計學意義(P=0.0200.05),其他染色體異常之間無相關性。1.3染色體異常與患者臨床資料之間的關系:1q21擴增與HGB降低有關(P=0.028);TP53與LDH升高有關(P=0.041),與首次化療后感染有關(P=0.017);D13S319與高年齡有關(P=0.020);IGH/CCND1與骨損傷數(shù)量增加有關(P=0.003),與白蛋白減少有關(P=0.049);IGH/FGFR3與白蛋白減少有關(P=0.010)。其他染色體異常與MM患者臨床資料無關。2 FISH結(jié)果與患者生存期關系隨訪至2017年1月1日13例(19.7%)患者死亡。FISH結(jié)果采用Kaplan-Meier法計算生存率并繪制生存曲線,單因素分析發(fā)現(xiàn)TP53陽性(8例)和陰性(53例),OS分別為28.250和42.605個月,PFS分別為17.857和28.415個月,具有統(tǒng)計學意義(P=0.027和P=0.045);1q21異常者(31例)PFS明顯短于正常者(30例),PFS為21.017和31.896個月,具有統(tǒng)計學意義(P=0.022),但OS無統(tǒng)計學差異(P=0.622);IGH/FGFR3異常者(9例)和正常者(50例),OS分別為17.889和41.672個月,PFS分別為12.063和28.757個月,具有統(tǒng)計學意義(P=0.037和P=0.025);IGH/MAF基因異常者(2例)和正常者(57例),OS分別為7.500和41.457個月,不具有統(tǒng)計學差異(P=0.137),PFS分別為4.000和28.518個月,具有統(tǒng)計學差異(P=0.000);D13S319基因異常者(25例)和正常者(36例)OS分別為39.926和37.926個月,PFS分別為28.466和19.270個月,差異無統(tǒng)計學意義(P=0.700和P=0.182)。將1q21探針檢測的61例患者分為三組:1q21陰性組、單純1q21陽性、1q21陽性并伴有其他染色體異常者,OS分別為43.618、24.314和13.500個月,無統(tǒng)計學差異(P0.05);PFS分別為31.896、20.400和8.125個月,1q21陰性組和單純1q21陽性之間存在統(tǒng)計學差異(P=0.038),其他無統(tǒng)計學差異(P0.05)。3臨床資料與患者生存期關系3.1 ISS、R-ISS分期與預后的關系:根據(jù)ISS分期,Ⅰ期5例,Ⅱ期23例,Ⅲ期38例,OS分別為41.000、34.436和35.775個月,Ⅰ期Ⅱ期Ⅲ期,PFS分別為23.250、27.647和25.768個月,差異均無統(tǒng)計學意義(P=0.918和P=0.918);根據(jù)R-ISS分期,Ⅰ期5例,Ⅱ期47例,Ⅲ期14例,OS分別為47.022、37.585和20.674個月;PFS分別為23.250、30.005和13.464個月,Ⅲ期PFS較Ⅰ期/Ⅱ期明顯縮短,差異均具有統(tǒng)計學意義(P=0.039和P=0.000);根據(jù)m SMART分期,OS低危41.771個月中危38.599個月高危22.111個月,PFS低危31.055個月中危20.045個月高危16.375個月,高危PFS較低危明顯縮短,差異均有統(tǒng)計學意義(P=0.036和P=0.010)。3.2臨床指標和預后的關系:HB100g/L較≥100g/L者OS為31.862和44.324個月,無統(tǒng)計學差異(P=0.136);PFS分別為20.935和30.552個月,具有統(tǒng)計學差異(P=0.020)。PLT100×109/L較≥100×109/L者OS明顯縮短,OS分別為11.906和43.738個月,具有統(tǒng)計學差異(P=0.000);PFS分別為15.641和28.029個月,無統(tǒng)計學差異(P=0.069)。LDH≥225U/L較225U/L者OS、PFS縮短,OS分別為23.375和44.601、PFS分別為15.631和29.217個月,具有統(tǒng)計學差異(P=0.003和P=0.002)。首次化療具有感染的患者OS較未感染的患者明顯縮短,分別為30.236和47.917個月,具有統(tǒng)計學意義(P=0.005);PFS無統(tǒng)計學差異(P=0.673)。3.3預后多因素分析發(fā)現(xiàn)m SMART高�；颊摺{細胞≥30%、PLT100×109/L、ALB35g/L、LDH≥225U/L可以使OS縮短;R-ISSⅢ期、HB100g/L、PLT100×109/L、Cr≥175umol/L、首次化療存在感染的患者PFS縮短。結(jié)論:1 FISH方法發(fā)現(xiàn)MM患者最常見的基因異常為IGH易位,染色體異常多發(fā)生在在14、1、13號染色體。2 D13S319陽性患者常伴隨IGH/FGFR3陽性。3 1q21擴增與HGB降低有關;TP53與LDH升高有關,與首次化療后感染有關;D13S319與高年齡有關;IGH/CCND1與骨損傷數(shù)量增加有關,與白蛋白減少有關;IGH/FGFR3與白蛋白減少有關。其他染色體異常與MM患者臨床資料無關。4 TP53、IGH/FGFR3和IGH/MAF是不良的預后因素,OS和PFS均具有統(tǒng)計學意義;D13S319 OS和PFS差異均無統(tǒng)計學意義;1q21陽性和陰性組PFS具有統(tǒng)計學意義,但OS無統(tǒng)計學差異;1q21陰性組和單純1q21陽性之間PFS存在統(tǒng)計學差異。5 ISS分期OS和PFS差異均無統(tǒng)計學意義;R-ISS分期OS和PFS差異均具有統(tǒng)計學意義;m SMART分期,高危OS和PFS較低危明顯縮短,差異均有統(tǒng)計學意義。6 HB100g/L較≥100g/L者OS無統(tǒng)計學差異,PFS具有統(tǒng)計學差異;PLT100×109/L較≥100×109/L者OS明顯縮短,OS具有統(tǒng)計學差異,PFS無統(tǒng)計學差異;LDH≥225U/L較225U/L者OS、PFS縮短,均具有統(tǒng)計學差異;首次化療具有感染的患者OS較未感染的患者明顯縮短,具有統(tǒng)計學意義,PFS無統(tǒng)計學差異。7預后多因素分析發(fā)現(xiàn)m SMART高�；颊�、漿細胞≥30%、PLT100×109/L、ALB35g/L、LDH≥225U/L可以使OS縮短;R-ISSⅢ期、HB100g/L、PLT100×109/L、Cr≥175umol/L、首次化療存在感染的患者PFS縮短。
[Abstract]:Objective: to detect the occurrence of chromosomal abnormalities in patients with multiple myeloma (multiple myeloma, MM) by Flurorescence in situ hybridization (FISH) and their relationship with the sex, age, staging, blood routine, biochemical and other clinical data, the effect and prognosis of the patients with multiple myeloma, and to clarify the risk stratification of the prognosis of the disease. Methods: the bone marrow specimens of 66 MM patients from February 1, 2013 to January 1, 2017 in the Department of Hematology, Third Hospital of Hebei Medical University, were collected to enrich the plasma cells by CD138 magnetic beads sorting. The specific probes (including 1q21, TP53, D13S319, IGH/CCND1, IGH/FGFR3, IGH/MAF probe) were used to detect the staining of 66 cases of MM patients. Results: 1 FISH results: the detection rate of 1.1 chromosome abnormality: in 66 cases of MM, 55 cases had chromosomal abnormalities, the total abnormal detection rate was 83.3% (55/66). The number of probe number more than 2 accounted for 56.1% (37/66), and the TP53 probe was used to detect the deletion of chromosome 17, the positive rate was 12.1% (8/66), and the IGH probe detected chromosome 14 abnormality, Yang The rate of sex was 54.5% (36/66), of which the positive rate of IGH/MAF was 3% (2/66), the positive rate of IGH/FGFR3 was 13.6% (9/66), and the positive rate of IGH/CCND1 was 25.8% (17/66); the chromosome deletion of chromosome 13 was detected with D13S319 probe and the positive rate of D13S319 was 40.9% (27/66). The 1q21 probe was used to detect chromosome 1, and the positive rate of 1q21 amplification was 47%. Relationship: D13S319 and IGH/FGFR3 chi square test found that D13S319 positive patients were often accompanied by IGH/FGFR3 positive, statistically significant (P=0.0200.05), other chromosomal abnormalities associated with the relationship between abnormal.1.3 chromosomes and the patient's clinical data: 1q21 amplification was associated with HGB reduction (P=0.028); TP53 was associated with LDH elevation (P=0.041), and first Infection related after secondary chemotherapy (P=0.017); D13S319 was associated with high age (P=0.020); IGH/CCND1 was associated with increased number of bone injuries (P=0.003), associated with albumin reduction (P=0.049); IGH/FGFR3 was associated with albumin reduction (P=0.010). Other chromosomal abnormalities were not related to clinical data in patients with MM; the relationship between.2 FISH and patient survival was followed up to 1 in 2017. On the 1 day, 13 cases (19.7%) patients died.FISH results using Kaplan-Meier method to calculate survival rate and draw survival curve. Single factor analysis found that TP53 positive (8 cases) and negative (53 cases), OS were 28.250 and 42.605 months respectively, PFS was 17.857 and 28.415 months respectively, with statistical significance (P=0.027 and P=0.045); 1q21 abnormal (31 cases) PFS obviously shorter than The normal (30 cases), PFS for 21.017 and 31.896 months, had statistical significance (P=0.022), but there was no statistical difference in OS (P=0.622); abnormal IGH/FGFR3 (9 cases) and normal (50 cases), OS were 17.889 and 41.672 months respectively, PFS was 12.063 and 28.757 months respectively, P=0.037 and P=0.025 (2 cases) and normal (2 cases) and normal. (57 cases), OS was 7.500 and 41.457 months respectively, with no statistical difference (P=0.137), PFS was 4 and 28.518 months, respectively, with statistical difference (P=0.000); D13S319 gene abnormal (25 cases) and normal (36 cases) OS were 39.926 and 37.926 months respectively, PFS was 28.466 and 19.270 months respectively, the difference was not statistically significant (P=0.700 and P=0.182). 61 patients with 1q21 probe were divided into three groups: 1q21 negative group, simple 1q21 positive, 1q21 positive and other chromosomal abnormality, OS was 43.618,24.314 and 13.500 months respectively, without statistical difference (P0.05); PFS was 31.896,20.400 and 8.125 months respectively, 1q21 negative group and simple 1q21 positive were statistically different (P=0.038), Other non statistical difference (P0.05).3 clinical data and patient survival relationship 3.1 ISS, the relationship between R-ISS staging and prognosis: according to ISS stage, stage I 5 cases, 23 cases in stage II, 38 cases in stage III, OS respectively 41.000,34.436 and 35.775 months, stage I stage III, PFS respectively 23.250,27.647 and 25.768 months, the difference is not statistically significant (P=0.918 and P=0. .918); according to R-ISS staging, 5 cases, 47 cases in stage II, 14 cases in stage III, OS for 47.022,37.585 and 20.674 months respectively; PFS was 23.250,30.005 and 13.464 months respectively. The stage III PFS was significantly shorter than phase I / II, the difference was statistically significant (P=0.039 and P=0.000), the root m SMART staging, and the low risk 41.771 months of OS low risk 38.599 months risk 22.111 The risk of high risk for 20.045 months was 16.375 months in the low risk of PFS 31.055 months, and the high risk of PFS was significantly shorter than that of low risk. The difference was statistically significant (P=0.036 and P=0.010).3.2 clinical indicators and prognosis: HB100g/L was more than 100g/L in OS for 31.862 and 44.324 months, with no statistical difference (P=0.136); PFS was 20.935 and 30.552 months, respectively. The study difference (P=0.020).PLT100 x 109/L was significantly shorter than that of 100 x 109/L, OS was 11.906 and 43.738 months respectively, with statistical difference (P=0.000); PFS was 15.641 and 28.029 months respectively. There was no statistical difference (P=0.069).LDH > 225U/L compared with 225U/L, 23.375 and 44.601 respectively, respectively, 15.631 and 29.217 months respectively. Statistical differences (P=0.003 and P=0.002). OS was significantly shorter in patients with infection than in uninfected patients, 30.236 and 47.917 months, respectively, with statistical significance (P=0.005). There was no statistical difference in PFS (P=0.673).3.3 prognosis multivariate analysis found that m SMART high risk patients, plasma cells more than 30%, PLT100 x 109/L, ALB35g/L, or more than It is possible to shorten OS, R-ISS III, HB100g/L, PLT100 * 109/L, Cr > 175umol/L, and PFS shortening in patients with infection in the first chemotherapy. Conclusion: the 1 FISH method found that the most common gene abnormality in MM patients is IGH translocation. Low related; TP53 is associated with elevated LDH, associated with first chemotherapy after chemotherapy; D13S319 is associated with high age; IGH/CCND1 is associated with increased number of bone injuries, associated with albumin reduction; IGH/FGFR3 is associated with albumin reduction. Other chromosomal abnormalities are not related to the clinical data of MM patients.4 TP53, IGH/FGFR3 and IGH/MAF are adverse prognostic factors, OS and PFS. There was no statistical significance in both D13S319 OS and PFS, while PFS in 1q21 positive and negative group had statistical significance, but there was no statistical difference between OS and 1q21 negative group and 1q21 positive. There was no statistical difference between.5 ISS and 1q21 positive..5 ISS stage OS and differences were not statistically significant. M SMART staging, high risk OS and PFS were significantly shorter than low risk. There was no statistical difference between.6 HB100g/L and 100g/L in OS, PFS had statistical difference, and PLT100 x 109/L was shorter than that of 100 x 109/L. Differences; OS was significantly shorter than those in uninfected patients for the first time chemotherapy. There was statistical significance. There was no statistical difference in PFS. The multivariate analysis of prognostic factors of.7 found that m SMART was more than 30%, PLT100 x 109/L, ALB35g/L, LDH > 225U/L could shorten the OS; PFS in patients with infection was shortened.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R733.3

【參考文獻】

相關期刊論文 前10條

1 梅建剛;李翰卿;曹紅琴;邵靚婧;翟勇平;;CD138磁珠分選結(jié)合間期熒光原位雜交在漿細胞病遺傳學診斷中的應用價值[J];中國實驗血液學雜志;2016年05期

2 楊毅;鄧玲;聶代蓉;陳永平;牟慶云;鐘暉;向靚;;多發(fā)性骨髓瘤遺傳學的研究進展[J];現(xiàn)代生物醫(yī)學進展;2016年26期

3 郭銳;李娟;龐纓;谷景立;馮瑩;謝瑋;;多發(fā)性骨髓瘤1號和11號染色體異常檢測及分析[J];廣東醫(yī)學;2016年06期

4 蔡可;黃紅銘;馬亞男;姜勝華;丁潤生;陸偉;沈毅;孫中偉;吳艷;;多發(fā)性骨髓瘤患者熒光原位雜交檢測遺傳學異常的回顧性分析[J];實用醫(yī)學雜志;2016年05期

5 翟冰;鄒丹丹;閆建軍;王楠;王莉莉;朱宏麗;黃文榮;于力;;熒光原位雜交檢測117例多發(fā)性骨髓瘤細胞遺傳學異常及預后分析[J];中國實驗血液學雜志;2016年01期

6 路瑾;黃曉軍;;高危多發(fā)性骨髓瘤之一——伴(4;14)易位多發(fā)性骨髓瘤[J];中國實用內(nèi)科雜志;2016年02期

7 王艷芳;王化;愪連永;劉彥;董菲;王繼軍;克曉燕;;利用FISH技術檢測多發(fā)性骨髓瘤不同類型標本分子細胞遺傳學異常[J];中國實驗血液學雜志;2015年05期

8 孫琦;安剛;劉恩彬;李占琦;張洪菊;楊晴英;孫福軍;馬躍;，

本文編號：1987463