本文選題：重型再生障礙性貧血　切入點：免疫抑制治療　出處：《北京協(xié)和醫(yī)學(xué)院》2015年碩士論文

【摘要】：目的：研究重型再生障礙性貧血(SAA)患者抗胸腺細胞球蛋白(ATG)聯(lián)合環(huán)孢素(CsA)治療后遲發(fā)性血液學(xué)反應(yīng)的發(fā)生率、治療前患者特征、血液學(xué)反應(yīng)(HR)質(zhì)量構(gòu)成及預(yù)后,比較免疫抑制治療(IST)應(yīng)時血液學(xué)反應(yīng)和遲發(fā)血液學(xué)反應(yīng)患者復(fù)發(fā)和晚期克隆性血液學(xué)異常特征,為一線IST后未達應(yīng)時血液學(xué)反應(yīng)患者進一步治療策略的制訂提供依據(jù)。方法：回顧性分析2002年至2013年533例一線行ATG (r-ATG/p-ATG)聯(lián)合CsA治療的SAA患者資料,設(shè)定IST后6個月內(nèi)獲得血液學(xué)反應(yīng)為應(yīng)時血液學(xué)反應(yīng),IST后6-12個月獲得血液學(xué)反應(yīng)為遲發(fā)血液學(xué)反應(yīng),分析遲發(fā)血液學(xué)反應(yīng)的發(fā)生率、血液學(xué)反應(yīng)質(zhì)量、復(fù)發(fā)、克隆性血液學(xué)異常和克隆性染色體異常及長期生存,并與應(yīng)時反應(yīng)組患者進行比較。對年齡≤40歲的患者HR質(zhì)量進一步分層分析,比較IST后6個月未獲HR患者與應(yīng)時反應(yīng)患者的長期生存。結(jié)果：(1)340例(63.79%,340/533)患者于IST后12個月內(nèi)獲得HR,其中295例(55.35%,295/533)患者IST后6個月內(nèi)獲血液學(xué)反應(yīng),45例(8.44%,45/533)患者6-12個月獲得血液學(xué)反應(yīng)。遲發(fā)血液學(xué)反應(yīng)患者占獲得血液學(xué)反應(yīng)患者的13.2%(45/340)和IST后6個月未緩解且未行挽救治療患者的29.03%(45/155)；(2)與應(yīng)時反應(yīng)患者比較遲發(fā)反應(yīng)患者中極重型再生障礙性貧血(VSAA)更多(57.8% vs 38.3%,p=0.013),外周血網(wǎng)織紅細胞(RET)%、RET絕對值以及中性粒細胞絕對值(ANC)均明顯更低(p值分別為p=0.000,p=0.000和p=0.006)；多因素分析網(wǎng)織紅細胞值為影響應(yīng)時和晚發(fā)血液學(xué)反應(yīng)的獨立影響因素(p=0.001),未發(fā)現(xiàn)IST后6個月時未獲血液學(xué)反應(yīng)患者在6-12個月間發(fā)生血液學(xué)反應(yīng)的影響因素；(3)IST后9個月、12個月及隨訪末期分析遲發(fā)反應(yīng)組患者血液學(xué)反應(yīng)質(zhì)量均明顯劣于應(yīng)時反應(yīng)組患者,統(tǒng)計學(xué)差異顯著(p=0.000,p=0.000和p=0.013)。在≤40歲患者中,遲發(fā)反應(yīng)組患者IST后不同時間點比較血液學(xué)反應(yīng)質(zhì)量也均明顯低于應(yīng)時反應(yīng)組患者(p=0.000,p=0.000和p=0.003)；(4)遲發(fā)反應(yīng)組患者5年OS為100%,應(yīng)時反應(yīng)組患者5年OS為98.2%(95% CI 97.4%-99.0%),統(tǒng)計學(xué)無顯著性差異(χ2=0.794,p=0.373)；遲發(fā)反應(yīng)組患者5年EFS 91.0%(95% CI86.7%-95.3%),應(yīng)時反應(yīng)組患者5年EFS 89.3%(95% CI 86.9%-91.7%),無明顯統(tǒng)計學(xué)差異(χ2=0.009,p=0.924)；(5).IST后6個月未獲得血液學(xué)反應(yīng)且未經(jīng)挽救治療患者的5年OS 77.70%(95%CI 72.905-82.50%),明顯低于應(yīng)時反應(yīng)組患者5年OS 98.2%(95% CI 97.4%-99.0%)(χ2=40.482,p=0.000)；IST后6個月未獲得血液學(xué)反應(yīng)患者的5年EFS 29.3%(95%CI 25.5%-33.1%),明顯低于應(yīng)時反應(yīng)組患者5年EFS 89.3%(95%CI 86.9%-91.7%)(x2值=207.038,p=0.000)。結(jié)論：(1).絕大多數(shù)SAA患者血液學(xué)反應(yīng)發(fā)生在IST后6個月內(nèi),遲發(fā)血液學(xué)反應(yīng)少見,占所有IST治療患者的8.44%；(2)遲發(fā)血液學(xué)反應(yīng)患者其IST前骨髓殘存造血較應(yīng)時血液學(xué)反應(yīng)患者可能更少；(3)遲發(fā)血液學(xué)反應(yīng)患者其血液學(xué)反應(yīng)質(zhì)量相對較差,近50%為部分反應(yīng),而長期生存與應(yīng)時血液學(xué)反應(yīng)患者無顯著性差異；(4)遲發(fā)血液學(xué)反應(yīng)患者占IST后6個月未獲血液學(xué)反應(yīng)患者的29.03%,與二次IST治療效果相近,故應(yīng)慎重評估二次治療時機及療效；(5)年齡40歲及以下患者一線治療無效選擇二次治療,應(yīng)首先考慮造血干細胞移植治療。
[Abstract]:Objective : To study the incidence of delayed hematological reactions in patients with severe aplastic anemia ( SAA ) after treatment with CsA . The results were as follows : ( 1 ) Hematological reaction was obtained in the patients with advanced hematological reactions after IST . The results were as follows : ( 1 ) There were 340 cases ( 63.79 % , 340 / 533 ) who received hematological reactions within 6 months after IST . Results : ( 1 ) The patients with late - onset hematological reactions accounted for 13 . 2 % ( 45 / 340 ) of patients with hematological reactions and 29 . 03 % ( 45 / 155 ) of untreated patients .
( 2 ) There were more severe aplastic anemia ( VSAA ) ( 57.8 % vs 38.3 % , p = 0 . 013 ) , reticulocyte ( RET ) % , RET absolute value and absolute neutrophil count ( ANC ) in peripheral blood reticulocyte ( RET ) % , RET absolute value and absolute neutrophil count ( ANC ) were significantly lower ( p = 0.000 , p = 0.000 and p = 0.006 ) .
Multivariate analysis of reticulocyte count was an independent prognostic factor ( p = 0.001 ) at the time of response to and late onset of hematological reactions , and no influence factors were found for hematological reactions between 6 and 12 months after IST 6 months .
( 3 ) After 9 months , 12 months and end - of - follow - up , the hematological reaction quality of patients with delayed reaction group was significantly worse than that in the response group ( p = 0.000 , p = 0.000 and p = 0 . 013 ) . In patients 鈮，

本文編號：1677508