[1]肖方,刘强,郭欢绪,等.供者型CIK细胞输注对清除异基因造血干细胞移植后微小残留病灶的疗效[J].第三军医大学学报,2016,38(12):1366-1370.
 Xiao Fang,Liu Qiang,Guo Huanxu,et al.Efficacy of donor-derived cytokine induced killer cells infusion for minimal residual diseases in patients after allogeneic stem cell transplantation[J].J Third Mil Med Univ,2016,38(12):1366-1370.
点击复制

供者型CIK细胞输注对清除异基因造血干细胞移植后微小残留病灶的疗效(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第12期
页码:
1366-1370
栏目:
专题报道
出版日期:
2016-06-30

文章信息/Info

Title:
Efficacy of donor-derived cytokine induced killer cells infusion for minimal residual diseases in patients after allogeneic stem cell transplantation
作者:
肖方刘强郭欢绪严学倩赵辉刘利
第四军医大学唐都医院血液内科
Author(s):
Xiao Fang Liu Qiang Guo Huanxu Yan Xueqian Zhao Hui Liu Li

Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, 710038, China

关键词:
造血干细胞移植细胞因子诱导的杀伤细胞微小残留病灶
Keywords:
allogeneic stem cell transplantation cytokine induced killer cells minimal residual diseases
分类号:
R617; R730.51; R733.7
文献标志码:
A
摘要:

目的      观察供者型细胞因子诱导的杀伤细胞(cytokine induced killer,CIK)细胞免疫治疗对异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后微小残留病灶(minimal residual disease,MRD)清除的疗效。      方法      回顾性分析我科2012年11月至2015年11月间的10例恶性血液病患者,其中急性淋巴细胞白血病5例,急性髓性白血病4例,慢性粒单细胞白血病1例。在allo-HSCT后出现分子生物学复发(7例)以及形态学复发(3例)后经减停免疫抑制剂、化疗、供者淋巴细胞输注等治疗后形态学缓解,但MRD仍阳性的患者,给予供者型CIK细胞输注治疗,分析其疗效。      结果      输注供者型CIK中位次数3(2~8)次。1例输注2次无效,最终血液学复发死亡;9例患者MRD转阴,其中1例输注10个月后再次复发死亡,1例因减停免疫抑制剂出现重度移植物抗宿主病死亡,另7例患者无病存活。输注CIK后中位随访时间为10(3~14)个月,中位生存时间8(3~14)个月,中位无病生存时间8(0~14)个月,其中5例患者输注CIK后无病生存时间长于移植后无病生存时间。      结论      供者型CIK细胞输注治疗对allo-HSCT后复发的患者可使其再次达到分子生物学缓解,减少血液学复发,提高造血干细胞移植疗效,且不良反应小。

Abstract:

Objective      To determine the clinica1 efficacy of infusions of donor-derived cytokine induced killer (CIK) cells in the patients having minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).       Methods      Ten refractory/relapsed patients, including acute lymphoblastic leukemia (ALL, n=5), acute myelogenous leukemia (AML, n=4), and chronic myelomonocytic leukemia (CMML, n=1) admitted in our department from November 2012 to November 2015 were enrolled in this retrospective analysis. All the patients were achieved molecular remission, then relapsed again after allo-HSCT, and 7 of them achieved MRD positive status and 3 relapsed. They had received salvage treatments including stopping immunosuppressive, chemotherapy and donor lymphocytes infusion. All patients were achieved remission but had MRD positive before CIK infusion.       Results      The median number of CIK infusions was 3 (ranged from 2 to 8) times. However, 1 case was no response to the twice infusions of CIK and died finally due to relapse. Nine patients of them achieved molecular responses after accepting the infusions of CIK. One of the 9 patients relapsed again and died 10 months after the infusions, one died of grade Ⅳ graft versus host disease after stopping immunosuppressive therapy, and the left 7 patients had stayed continuous complete remission (CCR). The median time of follow-up after CIK infusion was 10 (ranging from 3 to 14) months. The median time of overall survival (OS) was 8 months (ranging from 3 to 14), and that of event-free survival (EFS) was 8 months (ranging from 0 to 14). Five patients had longer remissions after infusion of CIK cells than after allo-HSCT.       Conclusion      Infusion of donor-derived CIK cells is an effective therapy for the MRD-positive patients after allo-HSCT, with well tolerance, achieving molecular remission, reducing relapse, and improving efficiency of hematopoietic stem cell transplantation.

参考文献/References:

[1]Sun J C, Pan K, Chen M S, et al. Dendritic cells-mediated CTLs targeting hepatocellular carcinoma stem cells[J]. Cancer Biol Ther, 2010, 10(4): 368-375.
[2]陈林, 史丽君, 陈姝, 等. 异基因造血干细胞移植联合供者CIK细胞过继免疫治疗复发难治血液肿瘤11例临床分析[J]. 第三军医大学学报, 2012, 34(24): 2449-2452.
[3]Laport G G, Sheehan K, Baker J, et al. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation[J]. Biol Blood Marrow Transplant, 2011, 17(11): 1679-1687. DOI: 10.1016/ j.bbmt.2011.05.012
[4]Kroger N, Zabelina T, van-Biezen A, et al. Allogeneic stem cell transplantation for myelodysplastic syndromes with bone marrow fibrosis[J]. Haematologica, 2011, 96(2): 291-297. DOI: 10.3324/haematol.2010.031229
[5]Lankester A C, Bierings M B, van-Wering E R, et al. Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation[J]. Leukemia, 2010, 24(8): 1462-1469. DOI: 10.1038/leu.2010.133
[6]Deol A, Lum L G. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited[J]. Cancer Treat Rev, 2010, 36(7): 528-538. DOI: 10.1016/j.ctrv.2010.03.004
[7]Yang B, Wang J, Cai L L, et al. Treatment of multiple solitary plasmacytomas with cytokine-induced killer cells[J]. Cytotherapy, 2014, 16(2): 278-284. DOI: 10.1016/j.jcyt.2013.11.001
[8]Kuci S, Rettinger E, Voss B, et al. Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation[J]. Haematologica, 2010, 95(9): 1579-1586. DOI: 10.3324/haematol.2009.019885
[9]Linn Y C, Niam M, Chu S, et al. The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies[J]. Bone Marrow Transplant, 2012, 47(7): 957-966. DOI: 10.1038/ bmt.2011.202
[10]Zhang Y, Wang J, Wang Y, et al. Autologous CIK cell immunotherapy in patients with renal cell carcinoma after radical nephrectomy[J]. Clin Dev Immunol, 2013, 2013: 195691. DOI: 10.1155/2013/195691
[11]Yu X, Zhao H, Liu L, et al. A randomized phase Ⅱ study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma[J]. J Clin Immunol, 2014, 34(2): 194-203. DOI: 10.1007/s10875-013-9976-0
[12]Nishimura R, Baker J, Beilhack A, et al. In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity[J]. Blood, 2008, 112(6): 2563-2574. DOI: 10.1182/blood-2007-06-092817

相似文献/References:

[1]陈林,史丽君,陈姝,等.异基因造血干细胞移植联合供者CIK细胞过继免疫治疗复发难治血液肿瘤11例临床分析[J].第三军医大学学报,2012,34(24):2449.
 Chen Lin,Shi Lijun,Chen Shu,et al.Allogeneic stem cell transplantation combined cytokine-induced-killer cells adaptive immunotherapy in treatment of refractory/relapsed hematologic neoplasms[J].J Third Mil Med Univ,2012,34(12):2449.
[2]刘季芳,刘枫,祁岩超,等.免疫编辑前后细胞因子诱导的杀伤细胞分泌细胞因子水平及细胞毒活性的比较[J].第三军医大学学报,2010,32(08):854.

更新日期/Last Update: 2016-06-07