儿童再生障碍性贫血造血干细胞移植相关并发症

doi:10.12372/jcp.2022.22e1706

Abstract

Abstract:

Aplastic anemia (AA) is a bone marrow hematopoietic failure disorder that is characterized by low bone marrow hematopoiesis, complete blood cytopenia and anemia/hemorrhage/infection syndrome. Allogeneic hematopoietic stem cell transplantation is currently an important method in the treatment of severe AA. The occurrence and management of transplant-related complications remain a great clinical challenge, and their prevention and treatment can directly affect the outcome of transplantation, long-term survival and quality of life of the children. In this paper, we review the diagnosis, prevention and treatment of common transplant complications during HSCT in children with AA, with the aim of improving the success rate and survival rate of these transplanted children.

Key words: aplastic anemia, allogeneic hematopoietic stem cell transplantation, complication, child

XU Jiawei, JIN Runming. Research progress in complications related to hematopoietic stem cell transplantation in children with aplastic anemia[J].Journal of Clinical Pediatrics, 2023, 41(3): 175-180.

Figures/Tables 1

References 41

[1]	Young NS. Aplastic anemia[J]. N Engl J Med, 2018, 379(17): 1643-1656. doi: 10.1056/NEJMra1413485
[2]	中华医学会血液学分会红细胞疾病贫血学组. 再生障碍性贫血诊断与专家共识(2017年版)[J]. 中华血液学杂志, 2017, 38(1): 1-5.
[3]	史红鱼, 程翼飞, 黄晓军, 等. 儿童单倍型造血干细胞移植后巨细胞病毒感染临床分析[J]. 中华血液学杂志, 2019, 40(5): 426-428.
[4]	中华医学会血液学分会干细胞应用学组. 异基因造血干细胞移植患者巨细胞病毒感染管理中国专家共识(2022年版)[J]. 中华血液学杂志, 2022, 43(8): 617-623.
[5]	黄晓军, 许兰平, 任汉云, 等. 异基因造血干细胞移植后巨细胞病毒病及其危险因素分析[J]. 中华医学杂志, 2003, 83(9): 766-769.
[6]	Khoury HJ, Wang T, Hemmer MT, et al. Improved survival after acute graft-versus-host disease diagnosis in the modern era[J]. Haematologica, 2017, 102(5): 958-966. doi: 10.3324/haematol.2016.156356 pmid: 28302712
[7]	Vigorito AC, Campregher PV, Storer BE, et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD[J]. Blood, 2009, 114(3): 702-708. doi: 10.1182/blood-2009-03-208983 pmid: 19470693
[8]	Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation[J]. Blood, 1998, 92(7): 2303-2314. pmid: 9746768
[9]	中华医学会血液学分会造血干细胞应用学组, 中国抗癌协会血液病转化委员会. 慢性移植物抗宿主病(cGVHD)诊断与治疗中国专家共识(2021年版)[J]. 中华血液学杂志, 2021, 42(4): 11.
[10]	Firoz BF, Lee SJ, Nghiem P, et al. Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis[J]. Arch Dermatol, 2006, 142(2): 175-182. pmid: 16490845
[11]	Levine JE, Braun TM, Harris AC, et al. A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study[J]. Lancet Haematol, 2015, 2(1): e21-e29. doi: 10.1016/S2352-3026(14)00035-0
[12]	中华医学会血液学分会干细胞应用学组. 中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅲ)——急性移植物抗宿主病(2020年版)[J]. 中华血液学杂志, 2020, 41(7): 529-536.
[13]	Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease[J]. N Engl J Med, 2021, 385(3): 228-238. doi: 10.1056/NEJMoa2033122
[14]	韩明哲. 异基因造血干细胞移植后植入功能不良研究进展[J]. 临床血液学杂志, 2019, 32(9): 660-664.
[15]	Sun YQ, He GL, Chang YJ, et al. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation[J]. Ann Hematol, 2015, 94(10), 1699-1705. doi: 10.1007/s00277-015-2440-x
[16]	师辰燕, Mamal A, 刘增慧, 等. 重型再生障碍性贫血行异基因造血干细胞移植后植入功能不良的危险因素分析[J]. 中华血液学杂志, 38(9): 761-766.
[17]	Lin F, Han T, Zhang Y, et al. The incidence, outcomes, and risk factors of secondary poor graft function in haploidentical hematopoietic stem cell transplantation for acquired aplastic anemia[J]. Front Immunol, 2022, 9: 896034.
[18]	Kong Y, Chang YJ, Wang YZ, et al. Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2013, 19(10): 1465-1473. doi: 10.1016/j.bbmt.2013.07.014
[19]	Hassan HT, Krog C, Stockschläder M, et al. Factors influencing haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis. A single-centre experience[J]. Support Care Cancer, 1997, 5(4): 299-306. pmid: 9257426
[20]	王佳丽, 韩明哲. 异基因造血干细胞移植后植入功能不良发生机制研究进展[J]. 中华血液学杂志, 2019, 38(9): 792-794.
[21]	Olivieri J, Mancini G, Goteri G, et al. Reversal of poor graft function with iron-chelating therapy after allogeneic transplantation for severe aplastic anemia[J]. Leuk Lymphoma, 2016, 57(4): 965-968. doi: 10.3109/10428194.2015.1085530
[22]	Visani G, Guiducci B, Giardini C, et al. Deferasirox improves hematopoiesis after allogeneic hematopoietie SCT[J]. Bone Marrow Transplant, 2014, 49(4): 585-587. doi: 10.1038/bmt.2013.213
[23]	Zhao Y, Gao F, Shi J, et al. Incidence, risk factors, and outcomes of primary poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2019, 25(9): 1898-1907. doi: 10.1016/j.bbmt.2019.05.036
[24]	Torok-Storb B, Boeckh M, Hoy C, et al. Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation[J]. Blood, 1997, 90(5): 2097-2102. pmid: 9292549
[25]	Kong Y. Poor graft function after allogeneic hematopoietic stem cell transplantation-an old complication with new insights[J]. Semin Hematol, 2019, 56(3): 215-220. doi: S0037-1963(18)30143-4 pmid: 31202433
[26]	Dvorak CC, Higham C, Shimano KA. Transplant-associated thrombotic microangiopathy in pediatric hematopoietic cell transplant recipients: a practical approach to diagnosis and management[J]. Front Pediatr, 2019, 7: 133. doi: 10.3389/fped.2019.00133 pmid: 31024873
[27]	中华医学会血液学分会造血干细胞应用学组. 造血干细胞移植相关血栓性微血管病诊断和治疗中国专家共识(2021年版)[J]. 中华血液学杂志, 2021, 42(3): 177-184.
[28]	Epperla N, Li A, Logan B, et al. Incidence, risk factors for and outcomes of transplant-associated thrombotic microangiopathy[J]. Br J Haematol, 2020, 189(6): 1171-1181. doi: 10.1111/bjh.16457
[29]	Jodele S, Davies SM, Lane A, et al. Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults[J]. Blood, 2014, 124(4): 645-653. doi: 10.1182/blood-2014-03-564997 pmid: 24876561
[30]	Laskin BL, Goebel J, Davies SM, et al. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy[J]. Blood, 2011, 118(6): 1452-1462. doi: 10.1182/blood-2011-02-321315 pmid: 21596850
[31]	Jodele S, Laskin BL, Dandoy CE, et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury[J]. Blood Rev, 2015, 29(3): 191-204. doi: 10.1016/j.blre.2014.11.001 pmid: 25483393
[32]	钱晓文, 翟晓文. 造血干细胞移植相关血栓性微血管病[J]. 中国小儿急救医学, 2022, 29(8): 577-583.
[33]	Harkensee C, Vasdev N, Gennery AR, et al. Prevention and management of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation--a systematic review and evidence-based guidance for clinical management[J]. Br J Haematol, 2008, 142(5): 717-731. doi: 10.1111/j.1365-2141.2008.07254.x
[34]	Hayden RT, Gu Z, Liu W, et al. Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients[J]. Transpl Infect Dis, 2015, 17(2): 234-241. doi: 10.1111/tid.12364 pmid: 25648430
[35]	Shepherd JD, Pringle LE, Barnett MJ, et al. Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow trans-plantation[J]. J Clin Oncol, 1991, 9(11): 2016-2020. pmid: 1941060
[36]	Fu H, Xu L, Liu D, et al. Late-onset hemorrhagic cystitis after haploidentical hematopoietic stem cell transplantation in patients with advanced leukemia: differences in ATG dosage are key[J]. Int J Hematol, 2013, 98(1): 89-95. doi: 10.1007/s12185-013-1350-8 pmid: 23632950
[37]	Xu LP, Zhang HY, Huang XJ, et al. Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease[J]. Chin Med J (Engl), 2007, 120(19): 1666-1671.
[38]	Olson A, Lin R, Marin D, et al. Third-Party BK virus-specific cytotoxic T lymphocyte therapy for hemorrhagic cystitis following allotransplantation[J]. J Clin Oncol, 2021, 39(24): 2710-2719. doi: 10.1200/JCO.20.02608
[39]	Saade A, Styczynski J, Cesaro S, et al. BK virus infection in allogeneic hematopoietic cell transplantation: an update on pathogenesis, immune responses, diagnosis and treatments[J]. J Infect, 2020, 81(3): 372-382. doi: S0163-4453(20)30390-X pmid: 32526327
[40]	Petca RC, Popescu RI, Toma C, et al. Chemical hemo-rrhagic cystitis: diagnostic and therapeutic pitfalls (Review)[J]. Exp Ther Med, 2021, 21(6): 624. doi: 10.3892/etm.2021.10056
[41]	何云燕. 造血干细胞移植后出血性膀胱炎的诊疗[J]. 临床儿科杂志, 2022, 40(1): 8-13.

Research progress in complications related to hematopoietic stem cell transplantation in children with aplastic anemia

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 1

References 41

Related Articles 15

Metrics

Comments

Recommended 0

[1]	LIN Jinfeng, CHEN Yi, DENG Yan, FENG Ai, HUANG Juan, CHEN Lizhu, XIE Jingqi, NIE Xiaojing. A comparative study on the detection of anti-Nephrin antibodies in children's nephrotic syndrome by chemiluminescence method and cell-based assay [J]. Journal of Clinical Pediatrics, 2026, 44(8): 682-689.
[2]	ZHENG Fangyuan, WANG Miao, DING Mingming, LU Aidong, JIA Yueping, ZENG Huimin, ZHANG Leping. Next-generation sequencing identified gene variants and their prognostic impact in pediatric Philadelphia chromosome positive acute lymphoblastic leukemia [J]. Journal of Clinical Pediatrics, 2026, 44(8): 690-697.
[3]	ZHANG Xiao, FANG Hongjun, KUANG Xiaojun, WANG Lijuan, WU Zhao, JIANG Sha, LI Pei, WU Liwen. Analysis of the clinical and electrophysiological characteristics of atonic seizures in children [J]. Journal of Clinical Pediatrics, 2026, 44(8): 698-704.
[4]	WANG Mengqian, YANG Hui. Case series analysis of 13 intestinal Behcet’s syndrome in children [J]. Journal of Clinical Pediatrics, 2026, 44(8): 705-711.
[5]	WU Xirong, GAO Qi, GUO Siyuan, YIN Qingqin, QIN Qiang, YIN Ju, JIAO Anxia, CHEN Chenghao, WU Di, WANG Bei, DUAN Xiaomin, PENG Yun, XU Baoping, GAO Liwei. Clinical characteristics and prognosis of pulmonary mucormycosis in children with diabetes mellitus [J]. Journal of Clinical Pediatrics, 2026, 44(8): 712-720.
[6]	HAN Yanan, GE Lanlan, CUI Jieyuan. A case report of branchio-oto-renal syndrome caused by EYA1 gene variant with a 6-year follow-up [J]. Journal of Clinical Pediatrics, 2026, 44(8): 721-726.
[7]	SHI Jiayi, GAO Chunlin, JIA Lili, LU Yunyun, SUN Tao, ZHU Xiaodong, XIA Zhengkun, ZHANG Pei. Phenotypic characteristics and prognostic analysis of a pedigree with childhood isolated nephrotic syndrome caused by compound heterozygous mutations in the COQ2 gene [J]. Journal of Clinical Pediatrics, 2026, 44(8): 727-732.
[8]	Rachel Rosen, Osvaldo Borrelli, Christophe Faure, Katja Karrento, Usha Krishnan, Samuel Nurko, Nathalie Rommel, Alan Silverman, Michiel van Wijk, Marc Benninga (Author), Chinese Medical Association Parenteral and Enteral Nutrition Branch Pediatrics Group, The Subspecialty Group of Gastroenterology, The Society of Pediatric, Chinese Medical Association, Gastroenterology Group, Pediatrician Branch, Chinese Medical Doctor Association (Translator). Core interpretation and explanation of Rome Ⅴ diagnostic criteria: upper gastrointestinal disorders of gut-brain interaction in children and adolescents [J]. Journal of Clinical Pediatrics, 2026, 44(7): 595-608.
[9]	Carlo Di Lorenzo, Miguel Saps, Bruno P. Chumpitazi, Shaman Rajindrajith, Annamaria Staiano, Nikhil Thapar, Miranda van Tilburg, Carlos Velasco-Benítez, Arine Vlieger (Author), Chinese Medical Association Parenteral and Enteral Nutrition Branch Pediatrics Group, The Subspecialty Group of Gastroenterology, The Society of Pediatric, Chinese Medical Association, Gastroenterology Group, Pediatrician Branch, Chinese Medical Doctor Association (Translator). Core interpretation and explanation of Rome Ⅴ diagnostic criteria: lower and biliary disorders of gut-brain interaction in children and adolescents [J]. Journal of Clinical Pediatrics, 2026, 44(7): 609-621.
[10]	LI Xufeng, TANG Haoxun, LI Xingjun, ZHANG Lize, GAO Chenqing, ZHAO Shunying, LIU Jianhua. Clinical characteristics, chest CT imaging phenotypes, and their correlation with prognosis in 76 children with Chlamydia pneumoniae pneumonia [J]. Journal of Clinical Pediatrics, 2026, 44(7): 622-627.
[11]	WANG Zhen, SHAO Jingbo, ZHANG Na, XIA Min, ZHU Jiashi, DU Chengkan, LI Hong. Factors influencing long-term recurrence in pediatric acute lymphoblastic leukemia patients with low-risk disease at initial diagnosis: a five-year follow-up analysis of 254 cases from a single center [J]. Journal of Clinical Pediatrics, 2026, 44(7): 628-635.
[12]	GUO Xuemei, XUE Yao, WANG Yongren, RONG Liucheng, FANG Yongjun, LIN Rufeng. Clinical features and prognosis of childhood acute myeloid leukemia with CBFA2T3::GLIS2 fusion [J]. Journal of Clinical Pediatrics, 2026, 44(7): 636-643.
[13]	YANG Lijun, FU Dongxia, CUI Yan, YANG Junmei, ZHANG Liming. Clinical manifestation and genetic analysis of CHARGE syndrome caused by CHD7 gene variation [J]. Journal of Clinical Pediatrics, 2026, 44(7): 644-650.
[14]	HU Yan, YANG Fan, LIANG Aimin, MAO Meng. Identification and management of faltering growth in children: insights from the 13th International Conference on Nutrition and Growth [J]. Journal of Clinical Pediatrics, 2026, 44(6): 485-488.
[15]	LIU Ziyao, WANG Congying, WANG Hongmao, ZHANG Mingming, XU Yingjie, LAI Jianming, NIU Wenquan, LI Xiaohui. Early differentiation of Kawasaki disease with joint symptoms and systemic juvenile idiopathic arthritis with Kawasaki disease-like symptoms: a single-center retrospective study [J]. Journal of Clinical Pediatrics, 2026, 44(6): 489-498.

组织活检有微血栓证据或满足以下7项指标中的5项
①乳酸脱氢酶（LDH）超过正常值上限
②蛋白尿（随机尿蛋白超过正常值上限或随机尿蛋白/肌酐≥2mg/mg
③高血压（年龄<18岁：血压高于同年龄、性别和身高的健康人群血压正常参考值的上限；年龄≥18岁：血压≥140/90mmHg）
④新发的血小板减少（血小板计数<50×10⁹/L或血小板计数较基线水平减少≥50%
⑤新发的贫血（血红蛋白值低于正常参考值下限或输血需求增加）
⑥微血管病变证据（外周血中存在破碎红细胞或组织标本病理学检查结果提示微血管病）
⑦终末补体活化（血浆sC5b-9值高于健康人群正常值上限）