本文選題：親緣性單倍體供體 + 臍血��； 參考：《蘇州大學(xué)》2014年碩士論文

【摘要】：異基因造血干細(xì)胞移植是根治兒童惡性血液病的主要方法。近年來(lái)隨著移植技術(shù)的進(jìn)步，親緣性單倍體作為重要的干細(xì)胞來(lái)源得到了廣泛的推廣運(yùn)用。本研究關(guān)注的是提高親緣性單倍體移植療效的臨床措施，對(duì)親緣性單倍體造血干細(xì)胞聯(lián)合無(wú)關(guān)臍血移植這一技術(shù)在治療兒童惡性血液疾病方面進(jìn)行可行性探討。 目的：評(píng)估應(yīng)用親緣性單倍體造血干細(xì)胞聯(lián)合無(wú)關(guān)臍血移植治療兒童惡性血液疾病的療效和安全性。 方法： 1，病例資料：對(duì)2012年8月到12月間6例惡性血液病兒童進(jìn)行了親緣性單倍體造血干細(xì)胞聯(lián)合無(wú)關(guān)臍血的移植。包括2例急性淋巴細(xì)胞性白血�。ˋLL），2例急性髓細(xì)胞性白血�。ˋML），1例慢性粒細(xì)胞性白血�。–ML）和1例重型再生障礙性貧血（SAA）。中位年齡10歲，中位體重38.3Kg。對(duì)供體使用粒細(xì)胞刺激因子（G-CSF）進(jìn)行動(dòng)員，取骨髓和外周血干細(xì)胞作為移植源，未進(jìn)行體外去除T細(xì)胞處理（TCD）。骨髓內(nèi)中位單個(gè)核細(xì)胞（MNC）數(shù)7.00（1.51~12.13）×108/Kg，中位CD34+細(xì)胞數(shù)1.81（1.23~2.45）×106/Kg，外周血中位單個(gè)核細(xì)胞數(shù)7.96（4.09~14.64）×108/Kg，中位CD34+細(xì)胞數(shù)5.85（2.74~14.20）×106/Kg。在骨髓干細(xì)胞輸注前4小時(shí)注射臍帶血，1天后輸注外周血干細(xì)胞。對(duì)受體應(yīng)用個(gè)體化的清髓性預(yù)處理，預(yù)處理方案為改良馬利蘭/環(huán)磷酰胺（BU/CY）或環(huán)磷酰胺/全身照射（CY/TBI）。移植后，每日計(jì)數(shù)血細(xì)胞，監(jiān)測(cè)造血重建。所有的受體均接受環(huán)胞霉素A、抗胸腺細(xì)胞球蛋白、霉酚酸酯和甲氨蝶呤（CsA+ATG+MMF+MTX）的強(qiáng)化聯(lián)合免疫抑制，預(yù)防移植物抗宿主�。℅VHD）。積極防治移植后其他并發(fā)癥。對(duì)患者進(jìn)行長(zhǎng)期隨訪。 2，移植前檢測(cè)：檢測(cè)供體的人類(lèi)白細(xì)胞抗原（HLA）-I、II類(lèi)抗體、主要組織相容性Ⅰ類(lèi)相關(guān)基因A（MICA）抗體、供受者的殺傷細(xì)胞免疫球蛋白樣受體（KIR）基因型，進(jìn)行移植前處理，提高移植成功率。 3、移植后檢測(cè)：檢測(cè)受者的短串聯(lián)重復(fù)序列（STR），確定嵌合情況，預(yù)測(cè)復(fù)發(fā)風(fēng)險(xiǎn)。 4、移植后并發(fā)癥防治：檢測(cè)巨細(xì)胞病毒CMV-PP65抗原、CMV-DNA、人乳頭瘤病毒（BKV）情況，早期預(yù)防，早期診斷，早期治療，減少移植后并發(fā)癥，降低嚴(yán)重程度。 結(jié)果： 1、1例患者存在HLA-I、II類(lèi)抗體陽(yáng)性，，移植前給予利妥昔單抗處理；所有患者M(jìn)ICA抗體均為陰性；2例患者存在KIR不相合，1例受體包含供體型。 2、移植后6例患者全部獲得供體型植入。中性粒細(xì)胞植入中位時(shí)間為11.8（10~15）天，血小板植入中位時(shí)間為14.2（12~16）天。監(jiān)測(cè)STR≥95%作為完全植入，其中位時(shí)間為18（14~21）天。 3、2例患者發(fā)生aGVHD，無(wú)重度aGVHD（III~IV度），無(wú)cGVHD發(fā)生。2例患者發(fā)生出血性膀胱炎（HC），其中1例存在多瘤病毒（BKV）感染。5例患者有巨細(xì)胞病毒（CMV）感染，其中3例病毒感染反復(fù)。1例患者并發(fā)侵襲性真菌感染（IFI）。無(wú)肝靜脈閉塞綜合癥（VOD）發(fā)生。 4、中位隨訪時(shí)間為376.5天（136~496），5例患者無(wú)病生存，僅1例重型再生障礙性貧血病人在移植后136天死于間質(zhì)性肺炎。 結(jié)論：親緣性單倍體供體骨髓及外周血干細(xì)胞聯(lián)合臍帶血移植可致移植物快速植入、低GVHD發(fā)生率和高無(wú)病生存率。
[Abstract]:The transplantation of allogeneic hematopoietic stem cells is the main method for the treatment of malignant hematopathy in children . In recent years , with the advancement of transplantation technology , the genetic haploid is widely used as an important source of stem cell . This study is concerned with the clinical measures to improve the curative effect of genetic haploid transplantation .

Objective : To evaluate the efficacy and safety of the application of the combined unrelated umbilical cord blood transplantation in the treatment of malignant hematologic diseases in children .

Method :

1 . Case data : The transplantation of peripheral blood stem cells with unrelated cord blood was carried out in 6 children with malignant hematopathy between August and December 2012 . The median age was 10 years , median body weight was 38.3Kg . Peripheral blood stem cells were harvested 4 hours before the infusion of bone marrow stem cells . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The graft versus host disease ( GVHD ) was prevented . All the recipients were followed up for long - term follow - up .

2 . Pre - transplantation detection : HLA - I and II antibodies of human leukocyte antigen ( HLA ) - I and II of donor were detected , and the main tissue - compatible class I - related gene A ( MICA ) antibody was detected , the genotype of killer cell immunoglobulin - like receptor ( KIR ) of the donor was genotyped , and the success rate of transplantation was improved .

3 . Detection after transplantation : Short tandem repeat sequence ( STR ) of the recipient is detected , the chimeric condition is determined , and the risk of recurrence is predicted .

4 . Prevention of complications after transplantation : Detection of cytomegalovirus CMV - PP65 antigen , CMV - DNA , human papillomavirus ( BKV ) , early prevention , early diagnosis , early treatment , reduced post - transplantation complications , and decreased severity .

Results :

1 . HLA - I and II antibodies were positive in 1 patient and rituximab was administered before transplantation .
All patients with MICA were negative ;
Two patients had a KIR mismatch and one receptor included donor type .

2 . All 6 patients received donor - type implantation . The median time of neutrophil implantation was 11.8 ( 10 - 15 ) days . The median time of platelet implantation was 14.2 ( 12 - 16 ) days . The monitoring STR 鈮

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