本文選題：FA5-BUCY預(yù)處理移植方案 + 惡性血液病　； 參考：《福建醫(yī)科大學(xué)》2015年碩士論文

【摘要】：背景:造血干細(xì)胞移植是部分惡性血液病患者獲得完全治愈的一種有效治療手段,但難治、復(fù)發(fā)和高危的惡性血液病患者可能因為對放、化療不敏感或不耐受失去接受干細(xì)胞移植的機(jī)會。此外,移植后疾病再發(fā)的高度風(fēng)險還可能導(dǎo)致移植的最終失敗。目的:觀察并分析FA5-BUCY預(yù)處理的挽救性造血干細(xì)胞移植治療高危、難治和復(fù)發(fā)急性白血病及骨髓增生異常綜合征的有效性和安全性。方法:回顧性分析2013年3月14日至2014年11月11日58例在我院接受FA5-BUCY預(yù)處理的挽救性造血干細(xì)胞移植治療的高危、難治和復(fù)發(fā)惡性血液病患者的臨床資料�；颊吣挲g在1歲-51歲之間,中位年齡23歲,男性43例,女性15例�；技毙运柘蛋籽�(AML)26例,骨髓增生異常綜合征(MDS)轉(zhuǎn)化AML 9例,急性淋巴細(xì)胞白血病(ALL)19例,高危(RCMD\RAEB\7q-)骨髓增生異常綜合征(MDS)3例,慢性粒細(xì)胞白血病加速期1例。其中高�；颊�25例,難治患者24例,復(fù)發(fā)患者9例,即疾病未緩解共有33例,骨髓中原幼細(xì)胞比例為7%-98%。接受親緣人類白細(xì)胞抗原(HLA)單倍型移植37例,非親緣HLA全相合移植3例,親緣HLA全相合移植17例,臍血移植1例。預(yù)處理方案均為FA5-BUCY,常規(guī)給予ATG、環(huán)孢素A、短程甲氨喋呤和嗎替麥考酚酯預(yù)防移植物抗宿主病,阿昔洛韋和靜脈丙種球蛋白預(yù)防性抗病毒,復(fù)方新諾明預(yù)防卡氏肺囊蟲病。根據(jù)既往有無真菌感染病史給予I級或II級預(yù)防性抗真菌治療。對于符合預(yù)防性供者淋巴細(xì)胞輸注標(biāo)準(zhǔn)的患者給予預(yù)防性輸注。58例患者在移植準(zhǔn)備階段均未發(fā)生嚴(yán)重感染或臟器功能衰竭。結(jié)果:除1例患者早期死亡,余57例患者移植過程均順利,回輸單個核細(xì)胞數(shù)的中位數(shù)為7.9×108/kg(2.2-21.4×108/kg),CD34+的干細(xì)胞數(shù)中位數(shù)為4.6×106/kg(1.8-20.6×106/kg),除外早期死亡患者,57例患者均植入成功,白細(xì)胞中位植活時間為回輸后13(9-25)天;血小板中位植活時間為移植后13(7-43)天,STR嵌合率檢測提示在植入期55例(96.5%)患者為完全嵌合狀態(tài),2例(3.5%)為混合嵌合狀態(tài),隨訪半年后患者均為完全嵌合狀態(tài)。 100天內(nèi)死亡率為15.5%,急性I-IV度GVHD發(fā)生率為48.3%,內(nèi)臟GVHD的發(fā)生率25.9%,慢性GVHD均為局限型,發(fā)生率為7.0%,病毒血癥發(fā)生率CMV為63.8%,EBV為84.5%,進(jìn)展為EBV病毒感染的發(fā)生率為1.7%。隨訪至今時間最長為2年,中位隨訪時間246.5天(12天-718天),2年內(nèi)復(fù)發(fā)率為17.5%,非復(fù)發(fā)死亡率為24.1%,總體生存率57.9%,無疾病生存率為53.3%,死亡原因主要為復(fù)發(fā)、GVHD和感染。影響移植后長期生存的主要因素有:移植后內(nèi)臟GVHD、CMV病毒血癥、回輸CD34+數(shù)量小于3.5×106個/kg。結(jié)論:FA5-BUCY預(yù)處理的挽救性造血干細(xì)胞移植為高危、難治和復(fù)發(fā)惡性血液病患者提供了移植機(jī)會,顯著改善移植預(yù)后,值得進(jìn)一步擴(kuò)大研究和延長隨訪觀察。
[Abstract]:Background: hematopoietic stem cell transplantation (HSCT) is an effective treatment for some patients with malignant hematologic diseases.Chemosensitivity or intolerance loses the chance of receiving stem cell transplantation.In addition, the high risk of disease recurrence after transplantation may lead to transplant failure.Objective: to observe and analyze the efficacy and safety of rescue hematopoietic stem cell transplantation (SCT) pretreated with FA5-BUCY in the treatment of high risk refractory and relapsed acute leukemia and myelodysplastic syndrome.Methods: from March 14, 2013 to November 11, 2014, 58 cases of high risk, refractory and recurrent malignant hematologic diseases were treated with FA5-BUCY pretreatment in our hospital.The patients ranged from 1 to 51 years old, with a median age of 23 years, 43 males and 15 females.There were 26 cases of acute myeloid leukemia, 9 cases of myelodysplastic syndrome (MDS) transformation, 19 cases of acute lymphoblastic leukemia (ALL), 3 cases of high risk myelodysplastic syndromes, 3 cases of myelodysplastic syndrome, 1 case of accelerated phase of chronic myelogenous leukemia.Among them, 25 cases were high risk, 24 cases were refractory, 9 cases were relapse, 33 cases were not relieved, and the proportion of primitive cells in bone marrow was 7- 98.37 cases of HLA-HLA haplotype transplantation, 3 cases of unrelated HLA homozygous transplantation, 17 cases of HLA homozygous transplantation and 1 case of umbilical cord blood transplantation were performed.The preconditioning regimen was FA5-BUCY.The routine administration of ATG, cyclosporine A, short course methotrexate and mycophenolate mofetil was used to prevent graft-versus-host disease, acyclovir and intravenous immunoglobulin were used to prevent the disease, and compound sulfamine was used to prevent pulmonary cysticercosis carinii.Grade I or II prophylactic antifungal therapy was given based on previous history of fungal infection.No severe infection or organ failure occurred in all 58 patients who met the criteria of preventive donor lymphocyte infusion during the preparation stage of transplantation.Results: with the exception of one patient who died early, the other 57 patients underwent successful transplantation. The median number of mononuclear cells was 7.9 脳 108/kg(2.2-21.4 脳 10 ~ (8)% 路kg ~ (34) 路kg ~ (34). The median number of stem cells was 4.6 脳 106/kg(1.8-20.6 脳 10 ~ (6)% 路kg ~ (-1) 路kg ~ (-1). All the 57 patients with early death were implanted successfully.The median survival time of leukocytes was 139-25 days after transfusion, and the median survival time of platelets was 137-43 days after transplantation. The detection of STR chimerism rate suggested that 55 patients were in complete chimeric state and 2 patients were in complete chimeric state.All patients were in complete chimerism after half a year follow-up.The mortality was 15.5d, the incidence of acute I-IV GVHD was 48.3, the incidence of visceral GVHD was 25.9, the incidence of chronic GVHD was 7.0, the incidence of viremia was 63.80.EBV was 84.5, the rate of progression to EBV virus infection was 1.7.The longest follow-up time was 2 years, the median follow-up time was 246.5 days, 12 days to 718 days, the recurrence rate was 17.5, the non-recurrence mortality was 24.1, the overall survival rate was 57.9 and the disease free survival rate was 53.3. The main causes of death were recurrent GVHD and infection.The main factors affecting the long-term survival after transplantation were as follows: visceral GV HDV CMV viremia, the number of CD34 was less than 3.5 脳 106 / kg.Conclusion the rescue hematopoietic stem cell transplantation pretreated with 10% FA5-BUCY is a high risk. Refractory and relapsed malignant hematologic diseases provide transplantation opportunities and improve the prognosis of transplantation. It is worthy of further study and extended follow-up observation.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R733.7;R551.3

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本文編號：1758163