含地西他滨预处理的异基因造血干细胞移植治疗难治复发急性髓性白血病的临床研究

发布时间：2018-06-22 17:35

本文选题：地西他滨 + 异基因造血干细胞移植　；参考：《中国人民解放军军事医学科学院》2017年硕士论文

【摘要】：第一部分含地西他滨预处理方案与标准预处理方案的异基因造血干细胞移植治疗难治复发急性髓性白血病的临床疗效比较目的评估地西他滨联合标准预处理方案异基因造血干细胞移植(allo-HSCT)治疗难治复发急性髓性白血病(AML)的可行性和安全性,降低移植后的复发率,改善难治复发AML的不良预后。方法回顾性地分析2006年4月至2016年5月于我科接受含地西他滨预处理方案与标准预处理方案allo-HSCT治疗的难治复发急性髓性白血病的临床特征及疗效。内容收集27例接受标准预处理方案(BU/CY或者CY/TBI)allo-HSCT治疗的难治复发AML患者作为对照组,20例接受高剂量地西他滨联合标准预处理方案及18例接受低剂量地西他滨联合标准预处理方案allo-HSCT治疗的难治复发AML患者作为实验组,观察患者的植入情况、移植相关死亡(TRM)、总生存(OS)率、无病生存(LFS)率及移植物抗宿主病(GVHD)的发生情况。结果标准预处理组、高剂量地西他滨组及低剂量地西他滨组患者的中性粒细胞以及血小板的中位植入时间分别为16(12-29)天和19(14-38)天、15(10-18)天和17.5(13-36)天、16(11-22)天和16.5(14-35)天,三组患者的中性粒细胞以及血小板的中位植入时间没有统计学差异(p0.05)。标准预处理组有1名患者死于移植相关并发症,移植相关死亡的累计发生率为4.2%。高剂量地西他滨组有4人死于移植相关并发症,其中因感染死亡3人,1人死于心脏猝死,移植相关死亡的累计发生率为25.2%;低剂量地西他滨组有5人死于移植相关并发症,其中因感染死亡3人,1人死于严重的GVHD,1人死于植入失败,移植相关死亡的累计发生率为30.2%;标准预处理组共17人发生aGVHD、其中Ⅱ-Ⅳ度aGVHD有14(52.8%)人,Ⅲ-Ⅳ度aGVHD有6人。高剂量地西他滨组共8人发生aGVHD,其中Ⅱ-Ⅳ度aGVHD有2(10%)人,Ⅲ-Ⅳ度aGVHD有0人;低剂量地西他滨组共10人发生aGVHD,其中Ⅱ-Ⅳ度aGVHD有7(45.3%)人,Ⅲ-Ⅳ度aGVHD有2人,其中1人死于激素耐药的重度aGVHD;标准预处理组患者的Ⅱ-Ⅳ度aGVHD的发生率明显高于高剂量地西他滨组,差异有统计学意义(p=0.0290.05),但与低剂量地西他滨组相比,没有发现统计学差异。标准预处理方案组、高剂量地西他滨理组和低剂量地西他滨组的1年总体生存(OS)率分别为22.2%,68.8%和27.8%(p=0.0070.05);标准预处理方案组、高剂量地西他滨组和低剂量地西他滨组的1年无病生存(LFS)率分别为22.2%,58.5%和20.8%(p=0.0230.05)。结论1、高剂量地西他滨用于移植标准预处理方案可能降低难治复发AML患者移植后Ⅱ-Ⅳ度aGVHD的发生率2、高剂量地西他滨联合标准预处理方案的allo-HSCT可以减少难治复发AML患者移植后的复发风险,提高患者的总体生存和无病生存,使患者生存获益第二部分地西他滨强化预处理与去甲氧柔红霉素强化预处理的异基因造血干细胞移植治疗难治复发急性髓性白血病的临床疗效比较目的分析地西他滨与去甲氧柔红霉素强化预处理方案造血干细胞移植(allo-HSCT)治疗难治复发急性髓性白血病(AML)的临床疗效方法回顾性地分析2009年7月至2016年5月于我科接受高剂量地西他滨(DAC)及去甲氧柔红霉素(IDA)强化预处理allo-HSCT治疗的44名难治复发AML患者的临床资料。内容收集接受高剂量地西他滨强化预处理allo-HSCT治疗的难治复发AML患者18人,接受去甲氧柔红霉素强化预处理allo-HSCT治疗的难治复发AML患者26人,两组患者移植前均处于未缓解状态。观察患者的植入情况、移植相关死亡(TRM)、总生存(OS)率、无病生存(LFS)率及移植物抗宿主病(GVHD)发生情况。结果接受强化预处理方案allo-HSCT治疗的44名难治复发AML患者均植入成功,地西他滨组中性粒细胞以及血小板的中位植入时间分别为15(10-18)天和18(13-36)天,去甲氧柔红霉素组中性粒细胞以及血小板的中位植入时间分别为14(12-22)天和19(14-35)天,两组患者中性粒细胞以及血小板中位植入时间没有发现统计学差异(p0.05)。地西他滨组有4(22.2%)人死于移植相关并发症,其中因感染死亡3人,1人死于心脏猝死,仅2(11.1%)人死于白血病复发;去甲氧柔红霉素组有2(7.7%)人死于移植后的感染并发症,9(34.6%)人死于白血病复发。高剂量地西他滨组共7(38.9%)人发生a GVHD,其中Ⅰ度2例,Ⅱ度5例,无一人发生Ⅲ-Ⅳ度a GVHD;去甲氧柔红霉素组共16(61.5%)人发生a GVHD,其中Ⅰ度9例,Ⅱ度6例,Ⅲ度1人,地西他滨组患者的a GVHD的发生率要低于去甲氧柔红霉素组,但差异无统计学意义(p0.05)。地西他滨组和去甲氧柔红霉素组的1年总体生存(OS)率分别为65.0%和57.7%,差异没有统计学意义(p=0.602);地西他滨组和去甲氧柔红霉素组的1年无病生存(LFS)率分别为53.5%和57.7%,差异无统计学意义(p=0.910)。结论1、地西他滨强化预处理方案allo-HSCT治疗难治复发AML是安全且有效的;2、地西他滨组a GVHD的发生率要低于去甲氧柔红霉素组,但由于我们此次的回顾性研究样本量较少,差异没有统计学意义;3、地西他滨用于强化预处理方案,可以取得不弱于去甲氧柔红霉素强化方案的临床疗效,且并没有增加预处理的毒性。
[Abstract]:The first part of the clinical efficacy of allogeneic hematopoietic stem cell transplantation with standard preconditioning regimen and standard preconditioning regimen for refractory and recurrent acute myelogenous leukemia: Objective To evaluate the treatment of refractory and relapsed acute myelogenous leukemia (AML) with allo-HSCT It is feasible and safe to reduce the recurrence rate after transplantation and improve the poor prognosis of refractory recurrent AML. Methods the clinical features and efficacy of 27 cases of refractory and recurrent acute myelopathy in our department from April 2006 to May 2016 were retrospectively analyzed. The clinical features and efficacy of 27 cases of refractory and recurrent acute myelopathy were analyzed. The refractory and relapsed AML patients received standard preconditioning (BU/CY or CY/TBI) allo-HSCT treatment as the control group, 20 patients received high dose of hitabine combined standard preconditioning and 18 cases of refractory relapsed AML patients treated with low dose western itabine combined standard preconditioning regimen as the experimental group, to observe the patient's implantation. Cases of transplant related death (TRM), total survival (OS), disease free survival (LFS) and graft-versus-host disease (GVHD). Results standard preconditioning group, high dose of hitabine group and low dose of low dose Xi tanbin group were 16 (12-29) days and 19 (14-38) days, 15 (10-18) days, respectively. With 17.5 (13-36) days, 16 (11-22) days and 16.5 (14-35) days, there was no statistical difference in the median implantation time of neutrophils and platelets in three groups (P0.05). There were 1 patients in the standard preconditioning group died of transplant related complications, and the cumulative incidence of transplantation related deaths was about 4 in 4.2%. high dose and 4 people died of transplant correlation. 3 people died of infection and 1 died of sudden cardiac death. The cumulative incidence of transplantation related deaths was 25.2%. 5 people died of transplant related complications in the low dose of the group. 3 of them died, 1 died of severe GVHD, 1 died of implantation failure, and the cumulative incidence of transplant related deaths was 30.2%; a standard preconditioning group shared a total of 30.2%. 17 people had aGVHD, of which there were 14 (52.8%) people with grade II - IV degree aGVHD and 6 degree aGVHD in grade III - IV degree. A total of 8 people were aGVHD in the high dose of hitabine group, of which 2 (10%) of aGVHD degree aGVHD had 2 (10%), and 0 of the degree III to IV degree, and 10 in the low dose to 10 people, of which there were 7 (45.3%) and III to IV degree aGVHD, among which there were 2 people, among which 1 died of excitement. The incidence of aGVHD in the standard pretreated group was significantly higher than that of the high dose of the seitribin group. The difference was statistically significant (p=0.0290.05), but there was no statistical difference compared with the low dose of selitabine group. The standard preconditioning regimen, the high dose of the West littoral group and the low dose of the West itabine group The 1 year overall survival (OS) rates were 22.2%, 68.8% and 27.8% (p=0.0070.05); the 1 year disease-free survival (LFS) rates of the high dose of the hitabine group and the low dose of the low dose of the hitabine group were 22.2%, 58.5% and 20.8% (p=0.0230.05). Conclusion 1. The high dose of hitabine for transplantation standard preconditioning regimen may reduce the recurrence of refractory recurrence. The incidence of II - IV degree aGVHD after transplantation of AML patients was 2. High dose of xitabine combined with standard preconditioning regimen could reduce the recurrence risk of refractory and relapsed AML patients after transplantation, improve the overall survival and disease free survival of the patients, and make the patient's survival benefit second parts of the fortified preconditioning and the strengthening of nordoxorubicin. Comparison of the clinical efficacy of pretreated allogeneic hematopoietic stem cell transplantation for refractory and recurrent acute myeloid leukemia objective analysis of the clinical efficacy of sxhitabine and allo-HSCT for refractory and relapsed acute myelogenous leukemia (AML) in the treatment of refractory and recurrent acute myelogenous leukemia (AML) in July 2009 To May 2016, the clinical data of 44 refractory recurrent AML patients treated with high dose of DAC and IDA enhanced preconditioning with allo-HSCT were received in our department. The content of 18 patients with refractory recurrent AML with high dose of xalbebin preconditioning allo-HSCT treatment was collected, and the fortified preconditioning of nordoxorubicin was received. 26 patients with refractory recurrent AML treatment were treated with allo-HSCT treatment. The two groups were in unremission state before transplantation. The patient's implantation, transplantation related death (TRM), total survival (OS), disease free survival (LFS) and graft-versus-host disease (GVHD) were observed. 44 refractory recurrent AML in allo-HSCT treatment with fortified preconditioning regimen. The implantation time of neutrophils and platelets in the group was 15 (10-18) days and 18 (13-36) days respectively. The median time of neutrophils and platelets were 14 (12-22) days and 19 (14-35) days, respectively, in the two group of neutrophils and platelets, and the time of implanting of neutrophils and platelets in the two group. There were no statistical differences (P0.05). 4 (22.2%) died of transplant related complications in the sxitabine group, of which 3 died of infection, 1 died of sudden cardiac death, and only 2 (11.1%) died of leukemia relapse; 2 (7.7%) died of infection complications after transplantation and 9 (34.6%) died of leukemia relapse. High dose XXX A total of 7 (38.9%) people in the riparian group had a GVHD, including 2 cases of degree I, 5 cases of degree II and no one degree a GVHD; 16 (61.5%) people of nordioxubicin group had a GVHD, of which 9 cases, 6 cases, and 1 people, and the incidence of a GVHD in the patients with dioxin group was lower than that of the daunorubicin group, but the difference was not statistically significant (P0.05). The difference was not statistically significant (P0.05). The total 1 year survival (OS) rate of the xitabine group and nordoxorubicin group was 65% and 57.7%, respectively, and the difference was not statistically significant (p=0.602). The 1 year disease-free survival (LFS) rate of the saxorubicin group and the dimethoxubicin group was 53.5% and 57.7%, respectively (p=0.910). Conclusion 1, p=0.602 preconditioning regimen allo-HS CT treatment for refractory AML is safe and effective; 2, the incidence of a GVHD in sxhitabine group is lower than that of nordoxorubicin group, but the difference is not statistically significant because of our retrospective study sample size, and 3. The bed was effective and did not increase the toxicity of preconditioning.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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