单倍体与同胞全相合造血干细胞移植治疗高危急性淋巴细胞白血病疗效观察

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目的分析异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,AlloHSCT)治疗高危急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的疗效,并探讨临床预后因素。方法对我院2007年7月至2013年8月进行Allo-HSCT治疗并随访2年以上的69例ALL患者进行临床分析。按移植方式分为单倍体组(n=42)和全相合组(n=27),对各组患者的临床特征及治疗转归进行回顾性分析,应用Kaplan-Meier法进行生存分析,COX回归模型进行多因素预后分析。结果单倍体组2年总体生存率(overall survival,OS)及2年无白血病生存率(leukemia-free survival,LFS)分别是63.4%、59.4%,而全相合组分别是53.9%、53.7%,两组间差异均无统计学意义(P>0.05);两组间2年累积非复发死亡率(cumulative non-relapse mortality,NRM)差异也无统计学意义(P>0.05);但2年累积复发率(cumulative relapse rate,RR)单倍体组明显高于全相合组(39.5%vs 19.5%,P=0.014)。造血重建方面,单倍体组中性粒细胞植入时间明显晚于全相合移植组(P=0.002),两组血小板植入时间无明显差异(P=0.072)。单倍体组Ⅰ~Ⅱ度急性移植物抗宿主病(graft-versus-host disease,GVHD)发生率明显高于全相合组(P=0.008),两组间Ⅲ~Ⅳ度急性GVHD及慢性GVHD发生率差异无统计学意义(P>0.05)。单倍体组半年内的感染率明显高于全相合组(P=0.02)。COX多因素分析显示患者移植前的疾病状态(非CR1)为异基因移植患者的危险因素(P=0.001),其危险度为7.581;而发生局限性慢性GVHD和初诊距离移植时间较短者为预后保护因素(P=0.013和P=0.012),危险度分别为0.178和0.688。结论在高危组ALL患者的治疗中,单倍体Allo-HSCT与全相合Allo-HSCT的整体疗效相当,因此,单倍体供者可以作为合适的造血干细胞来源。 Objective To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (AlloHSCT) in the treatment of high-risk acute lymphoblastic leukemia (ALL) and to explore the clinical prognostic factors. Methods The clinical data of 69 ALL patients who underwent Allo-HSCT from July 2007 to August 2013 in our hospital and were followed up for more than 2 years were analyzed. The patients were divided into two groups: haploid group (n = 42) and complete matched group (n = 27). The clinical characteristics and treatment outcome of each group were retrospectively analyzed. Survival analysis was performed by Kaplan-Meier method. COX Regression model for multivariate prognostic analysis. Results The 2-year overall survival (OS) and 2-year leukemia-free survival (LFS) of the haploid group were 63.4% and 59.4%, respectively, while that of the haplotype group was 53.9% and 53.7% (P> 0.05). There was also no significant difference in 2-year cumulative non-relapse mortality (NRM) between the two groups (P> 0.05). However, there was no significant difference between the two groups The cumulative relapse rate (RR) in haploid group was significantly higher than that in the all-matched group (39.5% vs 19.5%, P = 0.014). In hematopoietic reconstitution, haploid group neutrophil implantation time was significantly later than that of allograft transplantation group (P = 0.002). There was no significant difference in platelet engraftment time between the two groups (P = 0.072). The incidence of graft-versus-host disease (Ⅰ-Ⅱ) in the haploid group was significantly higher than that in the all-matched group (P = 0.008). The incidence of grade Ⅲ ~ Ⅳ acute GVHD and chronic GVHD The difference was not statistically significant (P> 0.05). The infection rate in haploid group within six months was significantly higher than that in all-matched group (P = 0.02). Cox multivariate analysis showed that the pre-transplant disease status (non-CR1) was a risk factor for allogeneic transplantation (P = 0.001), with a risk of 7.581; whereas, for patients with localized chronic GVHD and those who were initially diagnosed with distance transplants, those with shorter durations were Prognostic factors (P = 0.013 and P = 0.012) were 0.178 and 0.688, respectively. Conclusions The haploidentical Allo-HSCT is equivalent to the fully matched Allo-HSCT in high-risk ALL patients. Therefore, haploidentical donor can be a suitable source of hematopoietic stem cells.
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