本文選題：噬血細(xì)胞淋巴組織細(xì)胞增生癥 + 兒童��； 參考：《重慶醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的：噬血細(xì)胞淋巴組織細(xì)胞增生癥(hemophagocyticlyphohistiocytosis,HLH)，是一種免疫紊亂導(dǎo)致的以發(fā)熱、肝脾大、各類血細(xì)胞減低、高甘油三脂血癥或低纖維蛋白原血癥等為主要表現(xiàn)的多器官功能障礙，其特點(diǎn)是在骨髓、淋巴結(jié)或其他組織中可發(fā)現(xiàn)明顯的噬血現(xiàn)象，因而又稱噬血細(xì)胞綜合征(hemophagocytic syndrome，HPS)。HLH大多發(fā)生在兒童，分為家族遺傳性和非家族遺傳性，也被稱作原發(fā)性和繼發(fā)性，在這兩種形式，盡管化療和或免疫治療常常能獲得緩解，但其死亡率仍相當(dāng)高，原發(fā)性噬血仍需要干細(xì)胞移植來獲得永久緩解，而繼發(fā)性噬血可不通過移植得到緩解，大部分的死亡產(chǎn)生于未開始治療前。目前關(guān)于影響HLH預(yù)后的相關(guān)因素沒有較為統(tǒng)一的認(rèn)識(shí)。本文通過COX比例風(fēng)險(xiǎn)模型，收集HLH患兒的可能與預(yù)后相關(guān)的因素進(jìn)行單因素及多因素分析，探討預(yù)后相關(guān)的危險(xiǎn)因素，了解長(zhǎng)期生存可能性，為臨床早期判斷HLH患兒預(yù)后提供臨床依據(jù)。 方法：收集2008年1月至2012年12月期間于入住我院后確診為噬血細(xì)胞淋巴組織細(xì)胞增生癥的115例患兒的臨床及實(shí)驗(yàn)室指標(biāo)進(jìn)行回顧性分析。所有病例診斷均符合2004年修訂版HPS/HLH診斷標(biāo)準(zhǔn)。選擇年齡、性別、入院前發(fā)熱天數(shù)、病程中是否出現(xiàn)消化道出血(包括嘔血、血便或黑便，但除外大量鼻衄)、脾臟腫大、入院時(shí)的中性粒細(xì)胞計(jì)數(shù)、血小板計(jì)數(shù)、血紅蛋白、乳酸脫氫酶、初診血清白蛋白、谷丙轉(zhuǎn)氨酶、部分凝血活酶時(shí)間、纖維蛋白原、鐵蛋白、甘油三酯及NK細(xì)胞比值和治療中是否用激素、使用激素后體溫是否下降、是否使用環(huán)孢素A(cyclosporineA，CsA)、是否使用足葉乙甙(etoposide，VP16)等。所有患兒自入院之日起納入觀察病例，記錄相關(guān)數(shù)據(jù)，并對(duì)患兒的結(jié)局(死亡)進(jìn)行隨訪。采用SPSS17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析，生存分析采用Kaplan-Meier法。選用COX回歸分析方法對(duì)選取的研究因素進(jìn)行單因素和多因素分析，進(jìn)入及剔除標(biāo)準(zhǔn)為0.05，計(jì)算相對(duì)危險(xiǎn)度(relative risk,RR)。 結(jié)果： 1本研究中115例HLH患兒中有24例預(yù)后不良，其發(fā)生率為20.87％。發(fā)病年齡從6月～15歲不等，平均發(fā)病年齡4.6歲。24例預(yù)后不良的患兒中男性患兒9例，女性15例，男女比例1:1.67，均于確診后2月內(nèi)死亡，最短7天。 2單因素COX分析結(jié)果表明：協(xié)變量X4(消化道出血,p=0.00,RR=0.234)、協(xié)變量X12(初診時(shí)部分凝血活酶時(shí)間60s,p=0.00,RR=5.243)、協(xié)變量X13(血漿纖維蛋白原0.5g/L,p=0.00,RR=0.252)、 X18(使用激素后體溫是否下降,p=0.006,RR=0.129)與預(yù)后密切相關(guān)，有統(tǒng)計(jì)學(xué)意義(p0.05)；年齡、性別、入院前發(fā)熱天數(shù)、脾臟腫大(≥4cm)、入院時(shí)的中性粒細(xì)胞計(jì)數(shù)、血小板計(jì)數(shù)、血紅蛋白含量、谷丙轉(zhuǎn)氨酶升高(≥3倍正常值)、乳酸脫氫酶升高、鐵蛋白升高、甘油三酯升高、血清白蛋白降低及NK細(xì)胞比值減少，以及治療中是否使用激素、是否使用CsA、是否使用VP16等均無統(tǒng)計(jì)學(xué)意義(p0.05)，提示與預(yù)后無關(guān)。 3COX模型逐步剔除相關(guān)因素后，以p0.05為差異有統(tǒng)計(jì)學(xué)意義，篩選出有顯著意義的預(yù)后因素： X4(消化道出血,p=0.005,RR=3.276,95％CI=1.443-7.440)和X11(初診時(shí)部分凝血活酶時(shí)間60s,p=0.000,RR=5.803,95％CI=2.448-13.757)，且兩者均為相對(duì)獨(dú)立的危險(xiǎn)因素(B0, RR1)。 結(jié)論： 1本研究中HLH患兒預(yù)后不良發(fā)生率20.87％，男女比例1:1.67，女性多于男性，男性預(yù)后不良發(fā)生率為16.98％，女性預(yù)后不良發(fā)生率為24.19％。 2在病程合并消化道出血是預(yù)后不良的獨(dú)立危險(xiǎn)因素之一，合并消化道出血的患兒預(yù)后不良的風(fēng)險(xiǎn)為病程中無明顯消化道出血患兒的3.276倍，這為早期判斷預(yù)后及病程中治療觀察提供依據(jù)。 3HLH患兒在初診時(shí)APTT60s死亡風(fēng)險(xiǎn)為APTT60s患兒的5.803倍。凝血功能障礙患兒是獨(dú)立增加預(yù)后不良風(fēng)險(xiǎn)的因素之一，盡早糾正凝血功能障礙，減少臟器出血風(fēng)險(xiǎn)對(duì)改善預(yù)后有一定積極作用。 4單因素分析顯示使用激素后體溫是否下降可能于與預(yù)后不良發(fā)生密切關(guān)系，但多因素分析結(jié)果顯示無統(tǒng)計(jì)學(xué)意義。在治療中使用激素的病例模型中，1周內(nèi)體溫穩(wěn)定者預(yù)后較好(p=0.034,RR=4.781,95％CI=1.124-20.343)。 5單因素分析顯示初診時(shí)FIB0.5g/L可能與預(yù)后有密切關(guān)系，，但多因素分析并無統(tǒng)計(jì)學(xué)意義，與臨床工作總結(jié)不一致，故其相關(guān)性有待進(jìn)一步研究。 6HLH患兒初診時(shí)是否存在高乳酸血癥、低蛋白血癥、谷丙轉(zhuǎn)氨酶水平升高(≥3倍正常值)、高鐵蛋白血癥、高甘油三酯、NK細(xì)胞比值、及治療中是否使用激素、是否使用CsA、是否使用VP16對(duì)于生存時(shí)間無顯著影響。
[Abstract]:Objective: hemophagocytic lymphohistiocytosis (hemophagocyticlyphohistiocytosis, HLH) is an immune disorder caused by fever, liver and spleen, all kinds of hemocytosis, hyperglycerin three or hypoplasminemia, which are characterized by multiple organ dysfunction, characterized by bone marrow, lymph nodes, or other tissues. Hemophagocytic syndrome, HPS (HPS).HLH, also known as the family hereditary and non familial heredity, is also known as primary and secondary. In these two forms, although chemotherapy and immunotherapy are often remitted, the mortality rate is still high. Stem cell transplantation still requires stem cell transplantation for permanent remission, and secondary hemophagy can not be remission through transplantation, most of the deaths occur before untreated treatment. There is no more unified understanding of the related factors affecting the prognosis of HLH. This paper, through a COX proportional risk model, collects the possibility of the prognosis of children with HLH The factors were analyzed by single factor and multi factor analysis, the risk factors related to prognosis were discussed, and the long-term survival possibility was understood, which provided clinical evidence for the prognosis of HLH children in early clinical.
Methods: the clinical and laboratory indexes of 115 children diagnosed as hemophagocytic lymphohistiocytosis in our hospital from January 2008 to December 2012 were analyzed retrospectively. All the cases were in accordance with the revised HPS/HLH diagnostic criteria of 2004. Age, sex, the number of days before admission and the course of the disease. Hemorrhage of digestive tract (including hematemesis, stool or stool, except a large number of epistaxis), splenomegaly, neutrophils count, platelet count, hemoglobin, lactate dehydrogenase, first diagnosis of serum albumin, alanine aminotransferase, partial thromboplastin time, fibrinogen, ferritin, triglyceride and NK cells ratio and treatment are Whether or not the body temperature of the hormone, the use of hormones, the use of cyclosporin A (cyclosporineA, CsA), the use of etoposide (etoposide, VP16), etc. all children were included in the observation cases from the date of admission, recorded the relevant data, and followed up the outcome (death) of the children. Statistical analysis and survival analysis were carried out by SPSS17.0 software. The Kaplan-Meier method was used. Single factor and multi factor analysis were used to select the selected research factors with COX regression analysis. The entry and elimination standard was 0.05, and the relative risk degree (relative risk, RR) was calculated.
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本文編號(hào)：1923302