[采用降低强度预处理的异基因造血干细胞移植治疗p53基因异常的慢性淋巴细胞白血病（CLL）患者]
[Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in chronic lymphocytic leukemia (CLL) patients with the aberration of p53 gene].
作者信息
Wang Li, Miao Kourong, Fan Lei, Xu Ji, Wu Hanxin, Li Jianyong, Xu Wei
机构信息
The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2016 Apr;37(4):308-12. doi: 10.3760/cma.j.issn.0253-2727.2016.04.012.
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 0-11 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 investigated and applied widely in future.
目的
探讨减低剂量预处理异基因造血干细胞移植（RIC allo-HSCT）治疗伴有p53缺失的超高危慢性淋巴细胞白血病（CLL）患者的有效性和安全性，以加深对异基因造血干细胞移植治疗CLL的认识。
方法
本回顾性研究纳入了2012年7月至2014年1月期间在本中心接受治疗的4例伴有p53缺失的超高危CLL患者。采用RIC方案进行治疗，并评估造血重建、移植相关死亡率（TRM）、总生存期（OS）、无进展生存期（PFS）。
结果
我们登记了4例患者，中位年龄为56岁（49 - 61岁），其中男性3例，女性1例。单核细胞（MNC）和CD34(+)细胞的中位数分别为6.54（2.85 - 14.7）×10⁸/kg（受者体重）和5.81（2.85 - 7.79）×10⁶/kg（受者体重）。中性粒细胞恢复的中位时间为11天（9 - 12天），血小板恢复的中位时间为5.5天（0 - 11天）。3例患者（75%）在移植后第28天达到完全供者嵌合，1例（25%）为供者与受者的混合嵌合。在中位时间为26.5个月（21 - 39个月）的随访期间，2例（50%）患者发生了I级急性移植物抗宿主病（aGVHD），2例（50%）患者发生了巨细胞病毒（CMV）感染。有1例患者发生了带状疱疹病毒和EB病毒感染。4例患者均未发现移植相关死亡。1例部分缓解状态的患者在移植后5个月病情进展，其他3例患者在异基因造血干细胞移植后持续缓解。
结论
这些结果表明，RIC allo-HSCT显示出持久缓解、良好的耐受性和可接受的毒性，对于治疗伴有p53缺失的超高危CLL患者可能是一个更好的选择，值得在未来进行进一步研究和广泛应用。
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