异基因造血干细胞移植治疗儿童高IgM综合征的临床分析

doi:10.7499/j.issn.1008-8830.2112098

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摘要目的评估异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）治疗儿童高IgM综合征（hyper-IgM syndrome，HIGM）的疗效。方法回顾性收集行allo-HSCT的17例HIGM患儿的临床资料并进行分析，采用Kaplan-Meier法对移植后HIGM患儿进行生存分析。结果移植后，16例患儿临床诊断败血症；14例患儿在移植后100 d内病毒检测阳性，包括EB病毒11例、巨细胞病毒7例、JC病毒2例等；9例患儿存在侵袭性真菌病。急/慢性移植物抗宿主病分别有6例和3例。中位随访时间约为2年，3例患儿移植后早期死亡。患儿总生存（overall survival，OS）率、无事件生存（event-free survival，EFS）率和无病生存（disease-free survival，DFS）率分别为82.35%、70.59%和76.47%。log-rank检验结果显示，全相合移植患儿的EFS率高于不全相合移植患儿（P=0.019），全相合无关供者移植患儿的OS率、EFS率和DFS率均显著优于不全相合无关供者移植患儿（P<0.05），移植后无真菌感染患儿的EFS率与DFS率优于合并真菌感染患儿（P<0.05）。结论 allo-HSCT能有效治疗HIGM。接受全相合移植并积极防治真菌及机会性感染有助于改善患儿预后。

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关键词 ：高IgM综合征, 异基因造血干细胞移植, 原发性免疫缺陷病, 儿童

Abstract：Objective To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM). Methods A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT. Results After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (P=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (P<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (P=0.02) and DFS rate (P=0.04). Conclusions Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.

Key words： Hyper-IgM syndrome Allogeneic hematopoietic stem cell transplantation Primary immunodeficiency disease Child

收稿日期: 2021-12-21

通讯作者: 于洁，女，主任医师，教授。Email：1808106657@qq.com。 E-mail: 1808106657@qq.com

作者简介: 王子奇，男，硕士研究；

引用本文:

王子奇,孟岩,窦颖等. 异基因造血干细胞移植治疗儿童高IgM综合征的临床分析[J]. 中国当代儿科杂志, 2022, 24(6): 635-642.

WANG Zi-Qi,MENG Yan,DOU Ying et al. Clinical effect of allogeneic hematopoietic stem cell transplantation in children with hyper-IgM syndrome[J]. CJCP, 2022, 24(6): 635-642.

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	Qamar N, Fuleihan RL. The hyper IgM syndromes[J]. Clin Rev Allergy Immunol, 2014, 46(2): 120-130. PMID: 23797640. DOI: 10.1007/s12016-013-8378-7.
	Yazdani R, Fekrvand S, Shahkarami S, et al. The hyper IgM syndromes: epidemiology, pathogenesis, clinical manifestations, diagnosis and management[J]. Clin Immunol, 2019, 198: 19-30. PMID: 30439505. DOI: 10.1016/j.clim.2018.11.007.
	Leite LFB, Máximo TA, Mosca T, et al. CD40 ligand deficiency[J]. Allergol Immunopathol(Madr), 2020, 48(4): 409-413. PMID: 31831191. DOI: 10.1016/j.aller.2019.08.005.
	Meng X, Yang B, Suen WC. Prospects for modulating the CD40/CD40L pathway in the therapy of the hyper-IgM syndrome[J]. Innate Immun, 2018, 24(1): 4-10. PMID: 29132233. PMCID: PMC6830763. DOI: 10.1177/1753425917739681.
	Azzu V, Kennard L, Morillo-Gutierrez B, et al. Liver disease predicts mortality in patients with X-linked immunodeficiency with hyper-IgM but can be prevented by early hematopoietic stem cell transplantation[J]. J Allergy Clin Immunol, 2018, 141(1): 405-408.e7. PMID: 28756297. DOI: 10.1016/j.jaci.2017.06.036.
	Mitsui-Sekinaka K, Imai K, Sato H, et al. Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan[J]. J Allergy Clin Immunol, 2015, 136(4): 1018-1024. PMID: 25840720. DOI: 10.1016/j.jaci.2015.02.020.
	Ferrua F, Galimberti S, Courteille V, et al. Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study[J]. J Allergy Clin Immunol, 2019, 143(6): 2238-2253. PMID: 30660643. DOI: 10.1016/j.jaci.2018.12.1010.
	Wu J, Zhong W, Yin Y, et al. Primary immunodeficiency disease: a retrospective study of 112 Chinese children in a single tertiary care center[J]. BMC Pediatr, 2019, 19(1): 410. PMID: 31684895. PMCID: PMC6829960. DOI: 10.1186/s12887-019-1729-7.
	Xu L, Chen H, Chen J, et al. The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China-recommendations from the Chinese Society of Hematology[J]. J Hematol Oncol, 2018, 11(1): 33. PMID: 29495966. PMCID: PMC5833104. DOI: 10.1186/s13045-018-0564-x.
	Schoemans HM, Lee SJ, Ferrara JL, et al. EBMT-NIH-CIBMTR task force position statement on standardized terminology & guidance for graft-versus-host disease assessment[J]. Bone Marrow Transplant, 2018, 53(11): 1401-1415. PMID: 29872128. PMCID: PMC6786777. DOI: 10.1038/s41409-018-0204-7.
	Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report[J]. Biol Blood Marrow Transplant, 2015, 21(3): 389-401.e1. PMID: 25529383. PMCID: PMC4329079. DOI: 10.1016/j.bbmt.2014.12.001.
	Ozdemir ZN, CivrizBozda? S. Graft failure after allogeneic hematopoietic stem cell transplantation[J]. Transfus Apher Sci, 2018, 57(2): 163-167. PMID: 29724627. DOI: 10.1016/j.transci.2018.04.014.
	Armstrong AE, Smyth E, Helenowski IB, et al. The impact of high-resolution HLA-A, HLA-B, HLA-C, and HLA-DRB1 on transplant-related outcomes in single-unit umbilical cord blood transplantation in pediatric patients[J]. J Pediatr Hematol Oncol, 2017, 39(1): 26-32. PMID: 27820121. DOI: 10.1097/MPH.0000000000000690.
	14 黄晓军. 实用造血干细胞移植[M]. 2版. 北京: 人民卫生出版社, 2019: 24-34.
	Allewelt H, Martin PL, Szabolcs P, et al. Hematopoietic stem cell transplantation for CD40 ligand deficiency: single institution experience[J]. Pediatr Blood Cancer, 2015, 62(12): 2216-2222. PMID: 26291959. DOI: 10.1002/pbc.25711.
	Tsuji Y, Imai K, Kajiwara M, et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team[J]. Bone Marrow Transplant, 2006, 37(5): 469-477. PMID: 16435016. DOI: 10.1038/sj.bmt.1705273.
	Slatter MA, Rao K, Amrolia P, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience[J]. Blood, 2011, 117(16): 4367-4375. PMID: 21325599. DOI: 10.1182/blood-2010-10-312082.
	Veys P. Reduced intensity transplantation for primary immunodeficiency disorders[J]. Pediatr Rep, 2011, 3Suppl 2(Suppl 2): e11. PMID: 22053273. PMCID: PMC3206535. DOI: 10.4081/pr.2011.s2.e11.
	Ochs HD. Patients with abnormal IgM levels: assessment, clinical interpretation, and treatment[J]. Ann Allergy Asthma Immunol, 2008, 100(5): 509-511. PMID: 18517086. DOI: 10.1016/S1081-1206(10)60479-6.
	Imai K, Catalan N, Plebani A, et al. Hyper-IgM syndrome type 4 with a B lymphocyte-intrinsic selective deficiency in Ig class-switch recombination[J]. J Clin Invest, 2003, 112(1): 136-142. PMID: 12840068. PMCID: PMC162294. DOI: 10.1172/JCI18161.
	Du X, Tang W, Chen X, et al. Clinical, genetic and immunological characteristics of 40 Chinese patients with CD40 ligand deficiency[J]. Scand J Immunol, 2019, 90(4): e12798. PMID: 31179555. DOI: 10.1111/sji.12798.
	de la Morena MT, Leonard D, Torgerson TR, et al. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation[J]. J Allergy Clin Immunol, 2017, 139(4): 1282-1292. PMID: 27697500. PMCID: PMC5374029. DOI: 10.1016/j.jaci.2016.07.039.
	Adrianzen Herrera D, Ayyappan S, Jasra S, et al. Characteristics and outcomes of progressive multifocal leukoencephalopathy in hematologic malignancies and stem cell transplant—a case series[J]. Leuk Lymphoma, 2019, 60(2): 395-401. PMID: 29969336. DOI: 10.1080/10428194.2018.1474523.
	Steinhardt MJ, Wiercinska E, Pham M, et al. Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes[J]. J Transl Med, 2020, 18(1): 177. PMID: 32316991. PMCID: PMC7175555. DOI: 10.1186/s12967-020-02337-5.
	中国医师协会血液科医师分会, 中国侵袭性真菌感染工作组.血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则(第六次修订版)[J]. 中华内科杂志, 2020, 59(10): 754-763. PMID: 32987477. DOI: 10.3760/cma.j.cn112138-20200627-00624.
	Hardak E, Fuchs E, Geffen Y, et al. Clinical spectrum, diagnosis and outcome of rare fungal infections in patients with hematological malignancies: experience of 15-year period from a single tertiary medical center[J]. Mycopathologia, 2020, 185(2): 347-355. PMID: 32100219. DOI: 10.1007/s11046-020-00436-x.
	Spees LP, Martin PL, Kurtzberg J, et al. Reduction in mortality after umbilical cord blood transplantation in children over a 20-year period (1995-2014)[J]. Biol Blood Marrow Transplant, 2019, 25(4): 756-763. PMID: 30481599. PMCID: PMC6453734. DOI: 10.1016/j.bbmt.2018.11.018.
	Puerta-Alcalde P, Champlin RE, Kontoyiannis DP. How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease[J]. Blood, 2020, 136(24): 2741-2753. PMID: 33301030. PMCID: PMC7731790. DOI: 10.1182/blood.2020005884.