本文選題：造血干細胞移植　切入點：呼吸道感染　出處：《中山大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景 造血干細胞移植（hematopoietic stem cell transplantation，HSCT）已成為治療血液系統(tǒng)病、實體瘤、自身免疫性疾病和基因缺陷等疾病的重要手段之一。HSCT可增加呼吸道感染的發(fā)生幾率，其發(fā)生率可高達64.9%。HSCT后下呼吸道感染，尤其是真菌性肺炎的危險因素研究較為多見，但對HSCT后上呼吸道感染與下呼吸道感染的危險因素進行分層對比分析的文獻則較少。近年來人們關(guān)注到，HSCT后上呼吸道感染更易進展為下呼吸道感染，進而可危及移植后患者的生命，建議加強早期抗感染措施。 近年來，HSCT的臨床應(yīng)用正在逐漸擴大，其療效已得到肯定。但是，HSCT前后各種因素使得患者的機體防御能力受到損壞，易于發(fā)生各種感染，呼吸道組織結(jié)構(gòu)脆弱、血供豐富，因而成為移植后感染最常見的發(fā)生部位。HSCT后呼吸道感染的原因主要包括三方面：一、基礎(chǔ)疾病導(dǎo)致呼吸道感染的發(fā)生率增高；二、干細胞移植免疫抑制狀態(tài)導(dǎo)致呼吸道感染的發(fā)生率增高：移植預(yù)處理方案大劑量放-化療使患者的造血和免疫功能受到明顯破壞，在其骨髓恢復(fù)正常造血功能前，患者外周血細胞數(shù)極低，抵抗力差，使得機體對病原體高度易感，即使骨髓恢復(fù)造血功能后，免疫功能的重建也需要較長時間；三、移植物抗宿主反應(yīng)的發(fā)生使HSCT后呼吸道感染的發(fā)生率增高。移植物抗宿主�。╣raft versus host disease，GVHD）患者免疫失調(diào)和免疫重建延遲，使GVHD患者對病原體的抵抗力減弱，感染的發(fā)生率增高； GVHD對呼吸道粘膜完整性的損傷可使機體的固有免疫屏障損傷，病原體易于定植；GVHD的患者還可能因異體反應(yīng)淋巴細胞攻擊受者支氣管腺體，使其腺體分泌作用逐漸減弱，導(dǎo)致氣道干燥、免疫球蛋白分泌減少，對病原體的抵抗能力進一步下降，從而易發(fā)生呼吸道感染。 本文收集我院168例HSCT患者的資料，統(tǒng)計HSCT早期呼吸道感染率、呼吸道感染時間、呼吸道感染與造血重建的關(guān)系，并進行呼吸道感染、上呼吸道感染、下呼吸道感染危險因素的分析，希望對HSCT后呼吸道感染的早期診斷、治療起到一定的作用。移植早期是指HSCT后1至30天。HSCT后1至30天內(nèi)發(fā)生的呼吸道感染定義為移植早期呼吸道感染。 研究目的 1.總結(jié)HSCT早期呼吸道感染的發(fā)病情況； 2.探討HSCT早期造血重建情況與呼吸道感染的關(guān)系； 3.分析HSCT早期呼吸道感染的危險因素； 4.分層分析HSCT早期上、下呼吸道感染的危險因素。 研究對象與方法 1.研究對象 2000年-2010年在我院行HSCT的患者共168例。原發(fā)病類型包括：急性淋巴細胞白血病32例，急性非淋巴細胞白血病49例，地中海貧血44例，再生障礙性貧血12例，慢性淋巴細胞白血病3例，慢性粒細胞白血病9例，淋巴瘤5例，骨髓異常增生綜合癥2例，多發(fā)性骨髓瘤2例，復(fù)發(fā)性多軟骨炎4例，系統(tǒng)性紅斑狼瘡2例，假肥大性肌營養(yǎng)不良2例，粘多糖貯積病2例。年齡范圍為1歲至63歲，，其中兒童（＜14歲）101例，成年(≥14歲)67例，兒童與成年的比例約為1.51：1。男性患者104例，女性64例，男女比例約為1.63：1。經(jīng)統(tǒng)計分析，男女比例、年齡比例均存在可比性。 2.研究方法 2.1收集病例 2.1.1記錄造血干細胞移植患者的年齡、性別、疾病類型等基本資料； 2.1.1對患者的移植時間、移植方式、預(yù)處理方案、移植后造血恢復(fù)情況及HSCT早期呼吸道感染的發(fā)生情況進行回顧性病例對照研究。 2.2病例分組 將168例患者按照是否發(fā)生呼吸道感染分為呼吸道感染組和無呼吸道感染組，其中呼吸道感染組122人，無呼吸道感染組46人；呼吸道感染患者進一步分為上呼吸道感染組和下呼吸道感染組，其中上呼吸道感染組74人，下呼吸道感染組48人。 2.3統(tǒng)計分析 對符合正態(tài)分布的計量資料用均數(shù)±標準差（X|-±s）表示，兩組均數(shù)比較采用獨立樣本t檢驗；對不符合正態(tài)分布連續(xù)性計量資料用中位數(shù)及四分位數(shù)間距表示。計數(shù)資料應(yīng)用率或比表示，采用χ~2檢驗進行比較。危險因素分析先采用單因素分析篩選出有統(tǒng)計意義的可能危險因素，然后采用逐步前進法Logistic回歸分析得出獨立的危險因素。樣本量較少不宜進行危險因素分析的資料采用Spearson相關(guān)系數(shù)分析。所有數(shù)據(jù)統(tǒng)計分析均使用SPSS16.0軟件包進行分析，所以統(tǒng)計結(jié)果均以P0.05為有統(tǒng)計學(xué)差異。 結(jié)果 1.HSCT早期呼吸道感染率 2000年-2010年在我院接受HSCT的患者共168例，有122例患者在HSCT早期發(fā)生了呼吸道感染，呼吸道感染率為72.6%。上呼吸道感染共計74例，HSCT早期上呼吸道感染率為44.0%；下呼吸道感染共計48例，HSCT早期下呼吸道感染率為28.6%。2000年-2005年在我院接受HSCT的患者共59例，HSCT早期發(fā)生呼吸道感染的患者共52例，呼吸道感染率為88.1%；2006-2010在我院接受HSCT的患者共109例， HSCT早期發(fā)生呼吸道感染的患者共70例，呼吸道感染率為64.2%。將2000年-2005年與2006年-2010年患者HSCT早期呼吸道感染率比較，P值0.05，差異有統(tǒng)計學(xué)意義，近5年（2005-2010年）患者HSCT早期呼吸道感染率比前5年（2000-2005年）低。 2.HSCT早期造血重建情況及呼吸道感染時間 患者在HSCT早期造血重建的平均時間為移植后第14.5±5.4天。HSCT早期呼吸道感染時間的中位數(shù)為HSCT后第7天，四分位數(shù)間距為6.5天。發(fā)生呼吸道感染的122例患者中，99例患者呼吸道感染發(fā)生于造血重建前，占HSCT早期呼吸道感染的81.1%；23例患者呼吸道感染發(fā)生于造血重建后，占HSCT早期呼吸道感染的18.9%。 3. HSCT早期呼吸道感染的危險因素分析 根據(jù)單因素分析，年齡、干細胞來源、預(yù)處理方式、非親緣移植、HLA不匹配移植、血象恢復(fù)時間是HSCT早期呼吸道感染的危險因素（P＜0.05）。選擇單因素分析差異有統(tǒng)計意義的可能危險因素進行逐步前進法Logistic回歸分析，得出影響HSCT早期呼吸道感染的獨立危險因素有年齡、非親緣移植。 4. HSCT早期上呼吸道感染的危險因素分析 根據(jù)單因素分析，年齡、干細胞來源、非親緣移植、HLA不匹配移植、血象恢復(fù)時間是HSCT早期上呼吸道感染的危險因素（P＜0.05）。選擇單因素分析差異有統(tǒng)計意義的可能危險因素進行逐步前進法Logistic回歸分析，得出影響HSCT早期上呼吸道感染的獨立危險因素有年齡、非親緣移植。 5． HSCT早期下呼吸道感染的危險因素分析 根據(jù)單因素分析，干細胞來源、非親緣移植、HLA不匹配移植、aGVHD、真菌性肺炎病史是HSCT早期下呼吸道感染的危險因素（P＜0.05）。選擇單因素分析差異有統(tǒng)計意義的可能危險因素進行逐步前進法Logistic回歸分析，得出影響HSCT早期下呼吸道感染的獨立危險因素有真菌性肺炎病史、HLA不匹配移植。 6． HSCT早期下呼吸道感染的其他相關(guān)因素分析 經(jīng)Spearson相關(guān)系數(shù)分析得出，口腔潰瘍與下呼吸道感染存在正相關(guān)，相關(guān)系數(shù)r_s=0.178(P=0.047)。敗血癥與下呼吸道感染存在正相關(guān)，相關(guān)系數(shù)r_s=0.261(P=0.001)，但因病例數(shù)量較少，未能納入此次危險因素分析中。 結(jié)論 1.168例患者HSCT早期呼吸道感染率為72.6%，前5年患者HSCT早期呼吸道感染率比近5年高，感染率分別為88.1%和64.2%。 2. HSCT后患者造血重建的平均時間為移植后第14.5±5.4天。HSCT早期呼吸道感染的中位時間為移植后第7天。HSCT早期大多數(shù)呼吸道感染發(fā)生在造血重建恢復(fù)前。 3. HSCT早期呼吸道感染單因素分析的危險因素有年齡、干細胞來源、預(yù)處理方式、非親緣移植、HLA不匹配移植、血象恢復(fù)時間；多因素分析后獨立危險因素有年齡、非親緣移植。 4. HSCT早期上呼吸道感染單因素分析的危險因素有年齡、干細胞來源、非親緣移植、HLA不匹配移植、血象恢復(fù)時間；多因素分析后獨立危險因素有年齡、非親緣移植。 5. HSCT早期下呼吸道感染單因素分析的危險因素有干細胞來源、非親緣移植、HLA不匹配移植、發(fā)生aGVHD、真菌性肺炎病史；多因素分析后獨立的危險因素有HLA不匹配移植、真菌性肺炎病史。 6.敗血癥、口腔潰瘍的發(fā)生與HSCT早期下呼吸道感染存在正相關(guān)。
[Abstract]:Research background
Hematopoietic stem cell transplantation (hematopoietic stem cell transplantation, HSCT) has become the treatment of blood system disease, tumor, autoimmune diseases and genetic defects and other diseases is one of the important means of.HSCT can increase the probability of occurrence of respiratory tract infection, the incidence of lower respiratory tract infection can be as high as 64.9%.HSCT, especially the study of risk factors of fungal pneumonia the more common, but the hierarchical contrast analysis and risk factors of lower respiratory tract infection is less HSCT after upper respiratory tract infection. In recent years, people pay attention to HSCT after upper respiratory tract infection in lower respiratory tract infection more easily, and the quality and the life of patients after transplantation, proposed to strengthen the anti infection measures early.
In recent years, the clinical application of HSCT is gradually expanding, its efficacy has been confirmed. However, various factors of HSCT before and after the damage defense ability of the body makes patients, prone to infections, respiratory structure vulnerability, abundant blood supply, and thus become mainly includes three aspects of respiratory tract infection occurred after.HSCT. The most common cause of infection after transplantation: a basic disease causes respiratory tract infection rate increased; two, stem cell transplantation, immunosuppression resulted in increased incidence of respiratory tract infection: transplantation pretreatment regimen of high-dose chemotherapy and hematopoietic - make the immune function of the patients was significantly damaged in the recovery of bone marrow of normal hematopoietic function, peripheral blood of patients with the number of cells is extremely low, poor resistance, makes the body highly susceptible to pathogens, even if the recovery of bone marrow hematopoietic function after the reconstruction of the immune function also needs a long time. Three; incidence of graft-versus-host reaction to HSCT infection rate increased. Graft-versus-host disease (graft versus host disease, GVHD) in patients with immune disorders and delayed immune reconstitution, the GVHD patients with weakened resistance to pathogens, the infection rate increased; GVHD damage to the respiratory tract mucosa integrity the innate immune barrier can make damage to the body, easy to GVHD patients pathogen colonization; allogeneic lymphocyte response may also be due to attack by bronchial glands, the glands secretion gradually weakened, resulting in airway free drying, reduce the secretion of immunoglobulin, the resistance to pathogens decreased further, thus prone to respiratory infections.
This paper collected data of 168 cases with HSCT, statistical HSCT early infection rate of respiratory tract, respiratory tract infection time, the relationship between respiratory infection and hematopoietic reconstitution, and respiratory tract infection, upper respiratory tract infection, risk factors of lower respiratory tract infection, hope for the early diagnosis of respiratory tract infection after HSCT treatment, play a certain role. Refers to the definition of early transplantation occurred in 1 to 30 days after.HSCT for 1 to 30 days after HSCT transplantation for respiratory tract infection of respiratory tract infection early.
research objective
1. to summarize the incidence of early respiratory tract infection in HSCT.
2. to investigate the relationship between the early hematopoietic reconstitution of HSCT and the respiratory tract infection.
3. the risk factors of early respiratory tract infection in HSCT were analyzed.
4. stratified analysis of the risk factors for lower respiratory tract infection at the early stage of HSCT.
Research objects and methods
1. research objects
In 2000 -2010 years in our hospital 168 cases of HSCT. The primary disease types include: 32 cases of acute lymphocytic leukemia, 49 cases of acute non lymphocytic leukemia, 44 cases of thalassemia, 12 cases of aplastic anemia, 3 cases of chronic lymphocytic leukemia, chronic myeloid leukemia in 9 cases, 5 cases of lymphoma, 2 cases of myelodysplastic syndrome, 2 cases of multiple myeloma, 4 cases of relapsing polychondritis, 2 cases of systemic lupus erythematosus, Duchenne muscular dystrophy in 2 cases, 2 cases with mucopolysaccharidosis. The age range was 1 to 63 years old, the children (< 14 years) 101 cases that adult (over 14 years) in 67 cases, the proportion of children and adults about 104 cases of 1.51:1. patients, 64 cases were female, male to female ratio is about 1.63:1. by statistical analysis, the proportion of men and women, there are comparable in age.
2. research methods
2.1 collection of cases
2.1.1 records the basic data of age, sex, and type of disease in patients with hematopoietic stem cell transplantation.
2.1.1 retrospective analysis was performed on the time of transplantation, the way of transplantation, pretreatment plan, hematopoietic recovery after transplantation and the incidence of HSCT early respiratory infection.
2.2 cases group
The 168 patients with respiratory tract infection is divided into respiratory infection group and non respiratory infection group, respiratory tract infection group 122, group 46 without respiratory tract infection; patients were divided into group and group of lower respiratory tract infection of upper respiratory tract infection of respiratory tract infection, 74 of them were upper respiratory tract infection, 48 groups of lower respiratory tract infections..
2.3 statistical analysis
According to the measurement data of normal distribution with mean standard deviation (X|- + s) said that the two groups were compared using independent sample t test; do not conform to the normal distribution of continuous measurement data with a median and four percentile interval. Count data or application rate than that using X ~2 test comparative analysis of risk factors. By using single factor analysis to identify the possible risk factors with statistical significance, then using stepwise forward method Logistic regression analysis showed that independent risk factors. The small sample amount should not be carried out to analyze the risk factors of the data was analyzed by Spearson correlation statistical analysis. All data were analyzed using SPSS16.0 software package, so the statistical results are P0.05 as statistically significant.
Result
Early respiratory tract infection rate of 1.HSCT
In 2000 -2010 years in our hospital 168 cases of HSCT, 122 cases occurred in patients with respiratory tract infection in the early stage of HSCT, respiratory tract infection rate for a total of 74 cases of upper respiratory tract infection 72.6%., HSCT early upper respiratory tract infection rate was 44%; a total of 48 cases of lower respiratory tract infection, HSCT in the early stage of lower respiratory tract infection rate was 28.6%.2000 -2005 years in our hospital 59 cases of HSCT, HSCT in the early stage of respiratory tract infection occurred in patients with a total of 52 cases of respiratory tract infection rate was 88.1%; 2006-2010 in our hospital 109 cases of HSCT, HSCT in the early stage of respiratory tract infection occurred in patients with a total of 70 cases of respiratory tract infection rate was 64.2%. in 2000 -2005 and 2006 -2010 in patients with early HSCT respiratory tract infection rate, the P value is 0.05, the difference was statistically significant, nearly 5 years (2005-2010 years) in patients with early HSCT infection rate than the previous 5 years (2000-2005 years).
Early reconstruction of hematopoiesis and time of respiratory tract infection in 2.HSCT
The average HSCT in early hematopoietic reconstitution time for patients after transplantation, 14.5 + 5.4 days early.HSCT respiratory tract infection time for a median of seventh days after HSCT, the four percentile interval for 6.5 days. 122 cases of respiratory tract infection patients, 99 cases of patients with respiratory tract infection in hematopoietic reconstruction, early respiratory tract infection accounted for HSCT 81.1%; 23 cases of patients with respiratory tract infection in hematopoietic reconstruction after respiratory tract infection early 18.9%. accounted for HSCT
Analysis of risk factors for 3. HSCT early respiratory tract infection
According to the univariate analysis, age, source of stem cells, pretreatment, non genetic transplantation, HLA, transplantation, blood recovery time is a risk factor for respiratory tract infection early HSCT (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, factors that influence independent risk HSCT respiratory tract infection early age, non genetic transplantation.
Analysis of risk factors for early upper respiratory tract infection in 4. HSCT
According to the univariate analysis, age, source of stem cells, non genetic transplantation, HLA, transplantation, blood recovery time are risk factors of HSCT infection of the upper respiratory tract early (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, the independent risk factors for HSCT upper respiratory tract infection in early age, unrelated transplantation.
Analysis of risk factors for early lower respiratory tract infection in 5.HSCT
According to the analysis of single factor, stem cell source, unrelated transplantation, HLA, transplantation, aGVHD, history of fungal pneumonia was HSCT early in the risk factors of respiratory tract infection (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, the independent risk factors HSCT in the early stage of lower respiratory tract infection in patients with a history of fungal pneumonia, HLA mismatched transplantation.
Analysis of other related factors of lower respiratory tract infection in early 6.HSCT
The Spearson correlation coefficient analysis, oral ulcer and lower respiratory tract infection were positively correlated, the correlation coefficient r_s=0.178 (P=0.047) and lower respiratory tract infection. Sepsis has a positive correlation, the correlation coefficient r_s=0.261 (P=0.001), but the number of cases is less, not included in the analysis of the risk factors.
conclusion
The early respiratory infection rate of HSCT in 1.168 patients was 72.6%. The early respiratory infection rate of HSCT in the first 5 years was higher than that of nearly 5 years, and the infection rate was 88.1% and 64.2%., respectively.
After 2. HSCT, the average time of hematopoietic reconstitution was 14.5 + 5.4 days after transplantation. The median time of.HSCT infection was seventh days after transplantation. Most respiratory infections occurred before hematopoietic reconstitution in.HSCT.
3., the risk factors for single factor analysis of early respiratory tract infections in HSCT were age, stem cell origin, pretreatment, non related transplantation, HLA mismatch and hematologic recovery time. After multivariate analysis, the independent risk factors were age and non related transplantation.
4., the risk factors for single factor analysis of early HSCT upper respiratory tract infection were age, stem cell origin, non related transplantation, HLA mismatch and hematologic recovery time. After multivariate analysis, the independent risk factors were age and non related transplantation.
5., the risk factors of single factor analysis of HSCT early lower respiratory tract infection were stem cell origin, non related transplantation, HLA mismatch transplantation, aGVHD and fungal pneumonia history. Independent risk factors were HLA mismatched transplantation and fungal pneumonia history after multifactorial analysis.
6. septicemia, the occurrence of oral ulcers is positively related to the early lower respiratory tract infection in HSCT.

【學(xué)位授予單位】：中山大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R56

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