FA5-BUCY预处理的挽救性造血干细胞移植治疗高危难治复发白血病及骨髓增生异常综合征的疗效分析

发布时间：2018-04-16 08:39

本文选题：FA5-BUCY预处理移植方案 + 恶性血液病　；参考：《福建医科大学》2015年硕士论文

【摘要】：背景:造血干细胞移植是部分恶性血液病患者获得完全治愈的一种有效治疗手段,但难治、复发和高危的恶性血液病患者可能因为对放、化疗不敏感或不耐受失去接受干细胞移植的机会。此外,移植后疾病再发的高度风险还可能导致移植的最终失败。目的:观察并分析FA5-BUCY预处理的挽救性造血干细胞移植治疗高危、难治和复发急性白血病及骨髓增生异常综合征的有效性和安全性。方法:回顾性分析2013年3月14日至2014年11月11日58例在我院接受FA5-BUCY预处理的挽救性造血干细胞移植治疗的高危、难治和复发恶性血液病患者的临床资料。患者年龄在1岁-51岁之间,中位年龄23岁,男性43例,女性15例。患急性髓系白血病(AML)26例,骨髓增生异常综合征(MDS)转化AML 9例,急性淋巴细胞白血病(ALL)19例,高危(RCMD\RAEB\7q-)骨髓增生异常综合征(MDS)3例,慢性粒细胞白血病加速期1例。其中高危患者25例,难治患者24例,复发患者9例,即疾病未缓解共有33例,骨髓中原幼细胞比例为7%-98%。接受亲缘人类白细胞抗原(HLA)单倍型移植37例,非亲缘HLA全相合移植3例,亲缘HLA全相合移植17例,脐血移植1例。预处理方案均为FA5-BUCY,常规给予ATG、环孢素A、短程甲氨喋呤和吗替麦考酚酯预防移植物抗宿主病,阿昔洛韦和静脉丙种球蛋白预防性抗病毒,复方新诺明预防卡氏肺囊虫病。根据既往有无真菌感染病史给予I级或II级预防性抗真菌治疗。对于符合预防性供者淋巴细胞输注标准的患者给予预防性输注。58例患者在移植准备阶段均未发生严重感染或脏器功能衰竭。结果:除1例患者早期死亡,余57例患者移植过程均顺利,回输单个核细胞数的中位数为7.9×108/kg(2.2-21.4×108/kg),CD34+的干细胞数中位数为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,白细胞中位植活时间为回输后13(9-25)天;血小板中位植活时间为移植后13(7-43)天,STR嵌合率检测提示在植入期55例(96.5%)患者为完全嵌合状态,2例(3.5%)为混合嵌合状态,随访半年后患者均为完全嵌合状态。 100天内死亡率为15.5%,急性I-IV度GVHD发生率为48.3%,内脏GVHD的发生率25.9%,慢性GVHD均为局限型,发生率为7.0%,病毒血症发生率CMV为63.8%,EBV为84.5%,进展为EBV病毒感染的发生率为1.7%。随访至今时间最长为2年,中位随访时间246.5天(12天-718天),2年内复发率为17.5%,非复发死亡率为24.1%,总体生存率57.9%,无疾病生存率为53.3%,死亡原因主要为复发、GVHD和感染。影响移植后长期生存的主要因素有:移植后内脏GVHD、CMV病毒血症、回输CD34+数量小于3.5×106个/kg。结论:FA5-BUCY预处理的挽救性造血干细胞移植为高危、难治和复发恶性血液病患者提供了移植机会,显著改善移植预后,值得进一步扩大研究和延长随访观察。
[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.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.7;R551.3

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