Please wait a minute...
J Zhejiang Univ (Med Sci)  2018, Vol. 47 Issue (6): 651-658    DOI: 10.3785/j.issn.1008-9292.2018.12.14
    
Graft failure in allogeneic hematopoietic stem cell trans-plantation
CAO Liqin(),SHI Jimin*()
Center of Bone Marrow Transplantation, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Download: HTML( 10 )   PDF(1027KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

With the progress of medical technology, the development of new drugs and the improvement of the therapeutic effect of graft-versus host disease in the last two decades, the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been greatly improved. However, graft failure is still a rare but serious complication of allo-HSCT. HLA incompatibility, virus infection, elderly donor, uncontrolled primary disease, damage of bone marrow hematopoietic microenvironment, ABO blood group incompatibility, T cell depletion, reduced intensity conditioning, and low nucleated cell number are all risk factors for graft failure. In recent years, with the implementation of HLA haplo-identical hematopoietic stem cell transplantation, the role of donor-specific antibodies in graft failure has attracted attention increasingly. This article reviews the recent studies involving the mechanism, risk factors and prevention measures of graft failure in allo-HSCT.



Key wordsHematopoietic stem cell transplantation      HLA antigens/analysis      Antibody specificity      Living donors      Graft rejection      Risk factors      Review     
Received: 23 March 2018      Published: 15 March 2019
CLC:  R55  
Corresponding Authors: SHI Jimin     E-mail: 1401121270@qq.com;shijimin@zju.edu.cn
Cite this article:

CAO Liqin,SHI Jimin. Graft failure in allogeneic hematopoietic stem cell trans-plantation. J Zhejiang Univ (Med Sci), 2018, 47(6): 651-658.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2018.12.14     OR     http://www.zjujournals.com/med/Y2018/V47/I6/651


异基因造血干细胞移植植入失败研究进展

在过去20年里,随着医学技术和新药研制的发展,以及移植物抗宿主病疗效的提高,异基因造血干细胞移植(allo-HSCT)的预后得到了极大的改善,但植入失败仍是allo-HSCT术后面临的少见而严重的并发症。HLA不相合、病毒感染、供者高龄、原发病未缓解、骨髓造血微环境损伤、ABO血型不合、T细胞去除术、减剂量预处理方案、有核细胞数较低等均是导致植入失败的危险因素。近年来随着半相合造血干细胞移植的开展,供者特异性抗体在半相合植入失败中的作用引起关注。本文就近年来相关移植失败的机制、影响因素及其预防措施的研究进展作一综述。


关键词: 造血干细胞移植,  HLA抗原/分析,  抗体特异性,  活体供者,  移植物排斥,  危险因素,  综述 
[1]   MATTSSON J , RINGDéN O , STORB R . Graft failure after allogeneic hematopoietic cell transplantation[J]. Biol Blood Marrow Transplant, 2008, 14 (1 Suppl 1): 165- 170
[2]   KONGTIM P , CAO K , CIUREAS O . Donor specific anti-HLA antibody and risk of graft failure in haploidentical stem cell transplantation[J]. Adv Hematol, 2016, 2016:4025073
[3]   OLSSON R , REMBERGER M , SCHAFFER M et al. Graft failure in the modern era of allogeneic hematopoietic SCT[J]. Bone Marrow Transplant, 2013, 48 (4): 537- 543
doi: 10.1038/bmt.2012.239
[4]   NAKAMURA H , GRESS R E . Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow[J]. Transplantation, 1990, 49 (2): 453- 458
doi: 10.1097/00007890-199002000-00042
[5]   DONEY K , LEISENRING W , STORB R et al. Primary treatment of acquired aplastic anemia:outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle bone marrow transplant team[J]. Ann Intern Med, 1997, 126 (2): 107- 115
doi: 10.7326/0003-4819-126-2-199701150-00003
[6]   MURPHY W J , KUMAR V , BENNETT M . Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized[J]. J Exp Med, 1987, 166 (5): 1499- 509
doi: 10.1084/jem.166.5.1499
[7]   KIESSLING R , HOCHMAN P S , HALLER O et al. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts[J]. Eur J Immunol, 1977, 7 (9): 655- 663
doi: 10.1002/(ISSN)1521-4141
[8]   HUANG Y , REZZOUG F , CHILTON P M et al. Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells:a role for host NK cells in regulating HSC engraftment[J]. Blood, 2004, 104 (3): 873- 880
doi: 10.1182/blood-2003-11-3910
[9]   TAYLOR P A , EHRHARDT M J , ROFORTH M M et al. Preformed antibody, not primed T cells, is the initial and major barrier to bone marrow engraftment in allosensitized recipients[J]. Blood, 2007, 109 (3): 1307- 1315
[10]   王永翠.供者特异性抗体在肝移植中的临床研究[D].天津: 天津医科大学, 2016.
WANG Yongcui. The clinical research of donor specific antibody in liver transplantation[D]. Tianjin: Tianjin Medical University, 2016. (in Chinese)
[11]   BARGE A J , JOHNSON G , WITHERSPOON R et al. Antibody-mediated marrow failure after allogeneic bone marrow transplantation[J]. Blood, 1989, 74 (5): 1477- 1480
[12]   DAMMAN J , SEELEN M A , MOERS C et al. Systemic complement activation in deceased donors is associated with acute rejection after renal transplantation in the recipient[J]. Transplantation, 2011, 92 (2): 163- 169
doi: 10.1097/TP.0b013e318222c9a0
[13]   CIUREA S O , THALL P F , MILTON D R et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2015, 21 (8): 1392- 1398
doi: 10.1016/j.bbmt.2015.05.001
[14]   YOSHIHARA S , MARUYA E , TANIGUCHI K et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT[J]. Bone Marrow Transplant, 2011, 47 (4): 508- 515
[15]   LEFFELL M S , JONES R J , GLADSTONE D E . Donor HLA-specific Abs:to BMT or not to BMT?[J]. Bone Marrow Transplant, 2015, 50 (6): 751- 758
doi: 10.1038/bmt.2014.331
[16]   WANG J , XIA W , DENG J et al. Analysis of platelet-reactive alloantibodies and evaluation of cross-match-compatible platelets for the management of patients with transfusion refractoriness[J]. Transfus Med, 2018, 28 (1): 40- 46
doi: 10.1111/tme.2018.28.issue-1
[17]   TAN T W , KALISH J , FARBER A et al. Blood transfusion is associated with increased perioperative surgical site infection and graft failure in lower extremity bypass[J]. J Vasc Surg, 2011, 54:1227
[18]   SCOTT A , BUCKBY S , BAIDYA S et al. Platelet transfusion refractoriness pre-allograft is associated with higher rates of platelet non-engraftment and graft failure in adult allogeneic haematopoietic stem cell transplantation for haematological malignancies[J]. Blood, 2014, 124:1143
[19]   CIUREA S O , DE LIMA M , CANO P et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation[J]. Transplantation, 2009, 88 (8): 1019- 1024
doi: 10.1097/TP.0b013e3181b9d710
[20]   RUBINSTEIN P , CARRIER C , SCARADAVOU A et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors[J]. N Engl J Med, 1998, 339 (22): 1565- 1577
doi: 10.1056/NEJM199811263392201
[21]   GLADSTONE D E , BETTINOTTI M P . HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation:challenges and opportunities[J]. Hematology Am Soc Hematol Educ Program, 2017, 2017:645
[22]   LIANG Y , VAN ZANT G , SZILVASSYS J . Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells[J]. Blood, 2005, 106 (4): 1479- 1487
doi: 10.1182/blood-2004-11-4282
[23]   ARAI Y , KONDO T , YAMAZAKI H et al. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia[J]. Haematologica, 2016, 101 (5): 644- 652
doi: 10.3324/haematol.2015.139469
[24]   POGLIO S , CAHU X , UZAN B et al. Rapid childhood T-ALL growth in xenograft models correlates with mature phenotype and NF-κB pathway activation but not with poor prognosis[J]. Leukemia, 2015, 29 (4): 977- 980
doi: 10.1038/leu.2014.317
[25]   GADALLA S M , WANG T , HAAGENSON M et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia[J]. JAMA, 2015, 313 (6): 594- 602
doi: 10.1001/jama.2015.7
[26]   孙洁文, 胡成龙, 章骏 et al. 骨髓造血微环境对造血干细胞自我更新的调控[J]. 中华血液学杂志, 2014, 35 (6): 571- 574
SUN Jiewen , HU Chenglong , ZHANG Jun et al. Regulation of bone marrow microenvironment on hematopoietic stem cell self-renewal[J]. Chinese Journal of Hematology, 2014, 35 (6): 571- 574
[27]   陈峰, 吴德沛, 唐晓文 et al. 异基因造血干细胞移植治疗18例阵发性睡眠性血红蛋白尿症疗效分析[J]. 中华血液学杂志, 2015, 36 (12): 1005- 1010
CHEN Feng , WU Depei , TANG Xiaowen et al. Outcomes of allogeneic hematopoietic stem cell transplantation for 18 patients with paroxysmal nocturnal haemoglobinuria[J]. Chinese Journal of Hematology, 2015, 36 (12): 1005- 1010
doi: 10.3760/cma.j.issn.0253-2727.2015.12.005
[28]   OZDO?U H , YERAL M , BO?A C et al. Use of mesenchymal cells to modulate immune suppression and immune reconstruction in a patient with aplastic anemia complicated by invasive sino-orbital aspergillosis[J]. Turk J Haematol, 2014, 31 (2): 181- 183
[29]   NAVEIRAS O , NARDI V , WENZEL P L et al. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment[J]. Nature, 2009, 460 (7252): 259- 263
doi: 10.1038/nature08099
[30]   SAWADA A , INOUE M , KOYAMA-SATO M et al. Umbilical cord blood as an alternative source of reduced-intensity hematopoietic stem cell trans-plantation for chronic Epstein-Barr virus-associated T or natural killer cell lymphoproliferative diseases[J]. Biol Blood Marrow Transplant, 2014, 20 (2): 214- 221
doi: 10.1016/j.bbmt.2013.10.026
[31]   GOMES DE OLIVEIRA P G , UEDA M Y , REAL J M et al. Simultaneous quantification of the 8 human herpesviruses in allogeneic hematopoietic stem cell transplantation[J]. Transplantation, 2016, 100 (6): 1363- 1370
doi: 10.1097/TP.0000000000000986
[32]   WANG Z , SORROR M L , LEISENRING W et al. The impact of donor type and ABO incompatibility on transfusion requirements after nonmyeloablative haematopoietic cell transplantation[J]. Br J Haematol, 2010, 149 (1): 101- 110
doi: 10.1111/bjh.2010.149.issue-1
[33]   杨兵兵, 甘一峰, 陈鹏 et al. ABO血型不合对异基因造血干细胞移植的影响[J]. 中国实验血液学杂志, 2017, 25 (2): 535- 540
YANG Bingbing , GAN Yifeng , CHEN Peng et al. Effect of ABO-Incompatibility on outcome of allogeneic hematopoietic stem cell transplantation[J]. Journal of Experimental Hematology, 2017, 25 (2): 535- 540
[34]   KIMURA F , SATO K , KOBAYASHI S et al. Impact of AB0-blood group incompatibility on the outcome of recipients of bone marrow transplants from unrelated donors in the Japan Marrow Donor Program[J]. Haematologica, 2008, 93 (11): 1686- 1693
doi: 10.3324/haematol.12933
[35]   CLUZEAU T , LAMBERT J , RAUS N et al. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation:a study on behalf of SFGM-TC and SFHI[J]. Bone Marrow Transplant, 2016, 51 (5): 687- 691
doi: 10.1038/bmt.2015.351
[36]   SLOT S , SMITS K , VAN DE DONK N W et al. Effect of conditioning regimens on graft failure in myelofibrosis:a retrospective analysis[J]. Bone Marrow Transplant, 2015, 50 (11): 1424- 1431
doi: 10.1038/bmt.2015.172
[37]   MARFO K , LU A , LING M et al. Desensitization protocols and their outcome[J]. Clin J Am Soc Nephrol, 2011, 6 (4): 922- 936
doi: 10.2215/CJN.08140910
[38]   BALL L M , BERNARDO M E , ROELOFS H et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation[J]. Blood, 2007, 110 (7): 2764- 2767
doi: 10.1182/blood-2007-04-087056
[39]   PONTIKOGLOU C , DESCHASEAUX F , SENSEBé L et al. Bone marrow mesenchymal stem cells:biological properties and their role in hematopoiesis and hematopoietic stem cell transplantation[J]. Stem Cell Rev, 2011, 7 (3): 569- 589
doi: 10.1007/s12015-011-9228-8
[40]   MCNIECE I K , SHPALL E J . Ex vivo expansion of cord blood[M]. London: Springer London, 2009.
[41]   DI IANNI M , FALZETTI F , CAROTTI A et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation[J]. Blood, 2011, 117 (14): 3921- 3928
doi: 10.1182/blood-2010-10-311894
[42]   BERTAINA A , PITISCI A , SINIBALDI M et al. T cell-depleted and T cell-replete HLA-haploidentical stem cell transplantation for non-malignant disorders[J]. Curr Hematol Malig Rep, 2017, 12 (1): 68- 78
doi: 10.1007/s11899-017-0364-3
[43]   RIZZIERI D A , KOH L P , LONG G D et al. Partially matched, nonmyeloablative allogeneic transplantation:clinical outcomes and immune reconstitution[J]. J Clin Oncol, 2007, 25 (6): 690- 697
doi: 10.1200/JCO.2006.07.0953
[44]   VEYS P . Reduced intensity transplantation for primary immunodeficiency disorders[J]. Pediatr Rep, 2011, 3 (Suppl 2): e11
[45]   KEAN L S , HAMBY K , KOEHN B et al. NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative trans-plantation[J]. Am J Transplant, 2006, 6 (2): 292- 304
[46]   SCARADAVOU A , BRUNSTEIN C G , EAPEN M et al. Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia[J]. Blood, 2013, 121 (5): 752- 758
doi: 10.1182/blood-2012-08-449108
[47]   SERVAIS S , BEGUI Y , BARO F . Emerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation[J]. Expert Opin Emerg Drugs, 2013, 18 (2): 173- 192
doi: 10.1517/14728214.2013.798642
[48]   AVERSA F , TABILIO A , VELARDI A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype[J]. N Engl J Med, 1998, 339 (17): 1186- 1193
doi: 10.1056/NEJM199810223391702
[1] ZHAO Huihui,TANG Huifang. Research progress on composite animal models of inflammatory bowel disease based on gene knockout[J]. J Zhejiang Univ (Med Sci), 2018, 47(6): 665-670.
[2] TANG Hexiao,BAI Yuquan,SHEN Wulin,ZHAO Jinping. Research progress on interleukin-6 in lung cancer[J]. J Zhejiang Univ (Med Sci), 2018, 47(6): 659-664.
[3] XIANG Yilang,WU Ziheng,ZHANG Hongkun. Progress on in situ fenestration during thoracic endovascular aortic repair[J]. J Zhejiang Univ (Med Sci), 2018, 47(6): 617-622.
[4] LI Gaopeng,HE Jia,WANG Qingqing. Progress on cancer associated fibroblasts in tumor immunoregulation[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 558-563.
[5] YE Jianyu,SUN Ziyu,HU Weiwei. Roles of astrocytes in cerebral infarction and related therapeutic strategies[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 493-498.
[6] WANG Xiaoling,OUYANG Xumei,SUN Xiaoyi. Application of mesenchymal stem cells in antineoplastic drugs delivery for tumor-targeted therapy[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 525-533.
[7] HU Caiqin,ZHU Biao. Progress on pathogenesis of progressive multifocal leukoence-phalopathy[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 534-540.
[8] SHI Ting,YE Xiujin. Roles of CCAAT enhancer binding protein α in acute myeloblastic leukemia[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 552-557.
[9] HE Jiayi,ZHANG Xinmei. Research progress on oxidative stress in pathogenesis of endometriosis[J]. J Zhejiang Univ (Med Sci), 2018, 47(4): 419-425.
[10] XU Zhili,CUI Yiyi,LI Yan,GUO Yong. Research progress on nonspecific immune microenvironment in breast cancer[J]. J Zhejiang Univ (Med Sci), 2018, 47(4): 426-434.
[11] WANG Xingxing,WANG Panpan,YANG Xuyan. Research progress on systemic lupus erythematosus overlapping organ-specific autoimmune diseases[J]. J Zhejiang Univ (Med Sci), 2018, 47(4): 435-440.
[12] ZHANG Lifeng,ZHANG Xinmei. Research progress on roles of vitamin D in endometriosis[J]. J Zhejiang Univ (Med Sci), 2018, 47(4): 413-418.
[13] QIAN Bo,ZHANG Yanling,MO Xuming. Research progress on transcription factors and signal pathways involved in congenital esophageal atresia[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 239-243.
[14] ZHANG Xiaoyan,KANG Lijun. Molecular and cell biological mechanism of olfactory adaptation in Caenorhabditis elegans[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 307-312.
[15] TIAN Guangfeng,GAO Hui,HU Shasha,SHU Qiang. Research progress on genetic and epigenetic mechanisms in congenital heart disease[J]. J Zhejiang Univ (Med Sci), 2018, 47(3): 227-238.