减低强度预处理的异基因造血干细胞移植治疗伴p53基因异常的慢性淋巴细胞白血病  

Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in chronic lymphocytic leukemia （CLL） patients with the aberration of p53 gene

作　　者：王莉[1] 缪扣荣 范磊 许戟 吴汉新 李建勇 徐卫 

机构地区：[1]南京医科大学第一附属医院、江苏省人民医院,210029

出　　处：《中华血液学杂志》2016年第4期308-312,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81300408、81470329、81500125）;江苏高校优势学科建设工程项目（JXl0231801）;卫生公益性行业科研专项（201202017）;国家科技攻关项目（2014BAI09B12）;江苏省医学重点项目（BL2014086）

摘　　要：目的探讨减低强度预处理的异基因造血干细胞移植（RIC-allo-HSCT）治疗伴p53缺失的超高危慢性淋巴细胞白血病（CLL）的疗效及安全性，并提高allo-HSCT在CLL治疗中的认识。方法回顾性分析2012年7月至2014年1月进行同胞全相合供者RIC-allo-HSCT且伴p53缺失的4例超高危CLL患者资料，移植方式采用RIC方案，观察造血重建、移植相关并发症、总体生存（OS）、无进展生存（PFS）等临床指标。结果4例CLL患者中男3例，女1例，中位年龄56（49～61）岁。输注的中位单个核细胞（MNC）数为6.54（2.85～14.70）×10^8/kg，中位CD34^＋细胞数为5.81（2.85～7.79）×10^6/kg。4例患者移植后均获得快速而持久的造血重建，中性粒细胞和血小板植入时间分别为11（9～12）和5.5（0～11）d。造血重建后植活细胞嵌合鉴定证实3例为供者完全植入，1例为供受者混合植入。2例发生Ⅰ度急性移植物抗宿主病（GVHD），2例出现CMV感染，1例发生带状疱疹病毒及EB病毒血症，对症支持治疗后均好转；无移植相关死亡。中位随访时间为26.5（21～39）个月，3例完全缓解期行RIC-allo-HSCT的患者均无病生存，1例部分缓解期行移植的患者于移植后5个月发生疾病进展。结论伴p53缺失的超高危CLL患者对临床常规化疗敏感性差，生存期短；RIC-allo-HSCT对此类患者不良反应小并耐受性良好，临床缓解期长，值得进一步观察、推广。Objective To investigate the effectiveness and safety of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation （RIC allo-HSCT） in ultra high risk chronic lymphocytic leukemia （CLL） patients with the deletion of p53 to deepen the understanding of allo-HSCT in the treatment of CLL. Methods In this retrospective study, a total of 4 ultra high risk CLL patients with the deletion of p53 in our center between July 2012 and Jan 2014 were enrolled. The RIC regimen was administered and the hematopoietic reconstitution, transplantation related mortality （TRM）, overall survival （OS）, progress free survival （PFS） were evaluated. Results We registered 4 patients with the median age of 56 years （49-61 years）, including 3 males and 1 female. The median mononuclear cells （MNC） and CD34^＋ cells were 6.54 （2.85-14.7） ×10^8/kg （recipient body weight） and 5.81 （2.85-7.79） ×10^6/kg （recipient body weight）, respectively. The median time of the neutrophil recovery was 11 days （range of 9-12 days）, and the median time of the platelet recovery 5.5 days （range of 0-II days）. Three patients （75%） attained a full donor chimerism at day 28 after transplantation and one （25%） got a mixed chimerism of donor and recipient. During the follow-up at a median time of 26.5 months （range of 21-39 months）, 2 （50%） patients developed acute graft versus host disease （aGVHD） grade I and 2 （50%） patients got CMV infection. One patient got herpes zoster virus and EB virus infections. No transplantation related mortality was found in the 4 patients. One patient who was in partial response status progressed 5 months after transplantation, and the other 3 patients remained in durable remission after allo-HSCT. Conclusion These results suggested that RIC allo-HSCT showed durable remission, good tolerance and acceptable toxicity, which could be a better option for the treatment of ultra high risk CLL patients with the deletion of p53 and was worth to be i

关 键 词：白血病 淋巴细胞 慢性 P53基因 造血干细胞移植 异基因 

分 类 号：R733.72[医药卫生—肿瘤]