造血干细胞移植治疗儿童遗传性骨髓衰竭综合征疗效及预后分析

doi:10.12372/jcp.2025.24e0699

摘要/Abstract

摘要：

目的观察造血干细胞移植（HSCT）治疗儿童遗传性骨髓衰竭综合征（IBMFs）的疗效和预后。方法收集2019年1月至2023年11月在郑州大学第一附属医院行HSCT的IBMFs患儿的临床资料，分析其临床特征、移植预处理方案、造血重建情况以及预后。结果纳入IBMFs患儿18例，包括范可尼贫血（FA）7例、先天性角化不良（DKC）5例、先天性纯红细胞再生障碍性贫血（DBA）3例、先天性无巨核细胞性血小板减少症（CAMT）2例和重症先天性中性粒细胞减少症（SCN）1例，男10例、女8例，中位移植年龄为8.2（1.2~14.0）岁。移植后患儿中性粒细胞植入中位时间为11（9~21）天，血小板植入中位时间为13（10~30）天，18例患儿在中位随访10.6（1.0~62.9）个月时骨髓均为供者细胞完全嵌合状态。共8例患儿出现了急性移植物抗宿主病（GVHD），其中Ⅳ度2例、Ⅲ度2例、Ⅱ度1例、Ⅰ度3例；2例发生慢性GVHD，均为轻度。存活15例；死亡3例，2例FA患儿出现移植相关血栓性微血管病，应用血浆置换或去纤维蛋白多核苷酸治疗，效果欠佳，此2例患儿均死于多脏器衰竭；1例CAMT患儿移植后+28天出现严重肺部感染，病情进展迅速，死于呼吸衰竭。结论 HSCT是治疗儿童 IBMFs 的有效方法，根据IBMFs患儿所患疾病选择相适应的预处理方案可使患儿获得更好的疗效及预后。

关键词: 造血干细胞移植, 遗传性骨髓衰竭综合征, 预处理方案, 儿童

Abstract:

Objective To observe the efficacy and prognosis of hematopoietic stem cell transplantation (HSCT) in the treatment of inherited bone marrow failure syndromes (IBMFs) in children. Methods The clinical data of children with IBMFs who underwent HSCT in the First Affiliated Hospital of Zhengzhou University from January 2019 to November 2023 were collected, and their clinical characteristics, transplantation preconditioning regimen, hematopoietic reconstruction, and prognosis were analyzed. Results A total of 18 children with IBMFs were enrolled, including 7 cases of Fanconi anemia (FA), 5 cases of dyskeratosis congenita (DKC), 3 cases of Diamond-Blackfan anemia (DBA), 2 cases of congenital amegakaryocytic thrombocytopenia (CAMT) and 1 case of severe congenital neutropenia (SCN). There were 10 boys and 8 girls, with a median age of 8.2 (1.2-14.0) years. The median time of neutrophil engraftment was 11 (9-21) days, and the median time of platelet engraftment was 13 (10-30) days. During the median follow-up of 10.6 （1.0-62.9） months, the bone marrow of 18 patients was completely chimeric. A total of 8 patients developed acute graft-versus-host disease (GVHD), including 2 cases of grade Ⅳ, 2 cases of grade Ⅲ, 1 case of grade Ⅱ, and 3 cases of grade Ⅰ. Two children suffered from mild chronic GVHD. Fifteen patients survived and 3 died. Two children with FA developed transplant-related thrombotic microangiopathy, and they were treated with plasma exchange or defibrotide with poor results, and all died of multiple organ failure. One CAMT patient developed a severe pulmonary infection 28 days after transplantation, and his condition progressed rapidly, ultimately leading to respiratory failure. Conclusions HSCT is an effective method for the treatment of IBMFs in children. According to the different diseases of children with IBMFS, the appropriate preconditioning regimen can be selected to obtain a better curative effect and prognosis.

Key words: hematopoietic stem cell transplantation, inherited bone marrow failure syndrome, preconditioning regimen, child

中图分类号:

赵琳朝, 王英洁, 景沼贺, 买钰淼, 孙盼, 邱思敏, 牛宏运, 陈志伟, 董芃芃, 刘健. 造血干细胞移植治疗儿童遗传性骨髓衰竭综合征疗效及预后分析[J]. 临床儿科杂志, 2025, 43(7): 505-510.

ZHAO Linchao, WANG Yingjie, JING Zhaohe, MAI Yumiao, SUN Pan, QIU Simin, NIU Hongyun, CHEN Zhiwei, DONG Pengpeng, LIU Jian. Analysis of the efficacy and prognosis of hematopoietic stem cell transplantation for inherited bone marrow failure syndrome in children[J]. Journal of Clinical Pediatrics, 2025, 43(7): 505-510.

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参考文献 19

[1]	Lu Y, Xiong M, Sun RJ, et al. Hematopoietic stem cell transplantation for inherited bone marrow failure syndromes: alternative donor and disease-specific conditioning regimen with unmanipulated grafts[J]. Hematology, 2021, 26(1): 134-143.
[2]	Giudice V, Gurnari C, Pagliuca S, et al. Editorial: endocrinological sequelae of hematopoietic stem cell transplantation[J]. Front Endocrinol (Lausanne), 2023, 14: 1151213.
[3]	Pierri F, Faraci M, Giardino S, et al. Hematopoietic stem cell transplantation for classical inherited bone marrow failure syndromes: an update[J]. Expert Rev Hematol, 2021, 14(10): 911-925.
[4]	孙若楠, 李泊涵, 郑德菲, 等. 儿童异基因造血干细胞移植100天后闭塞性细支气管炎综合征临床特点及危险因素分析[J]. 临床儿科杂志, 2024, 42(2): 139-145.
	Sun RN, Li BH, Zheng DF, et al. Factors related to bronchiolitis obliterans syndrome in pediatric patients survived longer than 100 days after hematopoietic stem cell transplantation[J]. Linchuang Erke Zazhi, 2024, 42(2): 139-145.
[5]	罗明静, 余嘉明, 王晓东, 等. 424例地中海贫血患儿异基因造血干细胞移植后继发侵袭性真菌病临床分析[J]. 临床儿科杂志, 2025, 43(1): 21-28.
	Luo MJ, Yu JM, Wang XD, et al. Clinical analysis of invasive fungal disease secondary to allogeneic hematopoietic stem cell transplantation in 424 children with thalassemia[J]. Linchuang Erke Zazhi, 2025, 43(1): 21-28.
[6]	Elghetany MT, Punia JN, Marcogliese AN. Inherited bone marrow failure syndromes: biology and diagnostic clues[J]. Clin Lab Med, 2021, 41(3): 417-431. doi: 10.1016/j.cll.2021.04.014 pmid: 34304773
[7]	Peffault de Latour R, Peters C, Gibson B, et al. Recom-mendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes[J]. Bone Marrow Transplant, 2015, 50(9): 1168-1172.
[8]	Li Q, Luo C, Luo C, et al. Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes[J]. Ann Hematol, 2017, 96(8): 1389-1397. doi: 10.1007/s00277-017-3041-7 pmid: 28623394
[9]	Dignan FL, Clark A, Amrolia P, et al. Diagnosis and management of acute graft-versus-host disease[J]. Br J Haematol, 2012, 158(1): 30-45.
[10]	Dignan FL, Amrolia P, Clark A, et al. Diagnosis and management of chronic graft-versus-host disease[J]. Br J Haematol, 2012, 158(1): 46-61.
[11]	Balassa K, Danby R, Rocha V. Haematopoietic stem cell transplants: principles and indications[J]. Br J Hosp Med (Lond), 2019, 80(1): 33-39. doi: 10.12968/hmed.2019.80.1.33 pmid: 30592675
[12]	Chattopadhyay S, Lionel S, Selvarajan S, et al. Fludarabine-based low-intensity conditioning for Fanconi anemia is associated with good outcomes in aplastic anemia but not in MDS - a single-center experience[J]. Mediterr J Hematol Infect Dis, 2023, 15(1): e2023039.
[13]	Bhoopalan SV, Wlodarski M, Reiss U, et al. Reduced-intensity conditioning-based hematopoietic cell transplantation for dyskeratosis congenita: Single-center experience and literature review[J]. Pediatr Blood Cancer, 2021, 68(10): e29177.
[14]	Giardino S, Pierri F, Faraci M. How to optimize outcome of patients undergoing HLA-matched related haematopoietic stem cell transplantation in acquired and inherited bone marrow failure syndromes[J]. Br J Haematol, 2023, 203(2): 158-160.
[15]	Giri N, Ravichandran S, Wang Y, et al. Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder[J]. ERJ Open Res, 2019, 5(4): 0209-2019.
[16]	Bhoopalan SV, Suryaprakash S, Sharma A, et al. Hematopoietic cell transplantation and gene therapy for Diamond-Blackfan anemia: state of the art and science[J]. Front Oncol, 2023, 13: 1236038.
[17]	Liu Y, Karlsson S. Perspectives of current understanding and therapeutics of Diamond-Blackfan anemia[J]. Leukemia, 2024, 38(1): 1-9.
[18]	Bartels M, Bierings M. How I manage children with Diamond-Blackfan anaemia[J]. Br J Haematol, 2019, 184(2): 123-133.
[19]	Aladağ E, Kelkitli E, Göker H. Acute graft-versus-host disease: a brief review[J]. Turk J Haematol, 2020, 37(1): 1-4. doi: 10.4274/tjh.galenos.2019.2019.0157 pmid: 31475512

患儿	疾病	干细胞来源	预处理方案¹⁾	MNC/×10⁸·kg^-1	CD34⁺/×10⁶·kg^-1	中性粒细胞植入/d	血小板植入/d
例1	FA	PBSC	Bu8+Flu200+Cy40+ATG10	12.31	11.64	9	10
例2	FA	PBSC	Bu8+Flu160+Cy40+ATG10	17.00	8.90	11	16
例3	FA	PBSC	Bu8+Flu160+Cy40+ATG10	9.75	9.35	11	17
例4	FA	PBSC	Flu160+Cy40+ATG10	11.20	2.20	10	13
例5	FA	PBSC	Flu160+Cy40+ATG10	4.90	2.50	10	11
例6	FA	PBSC	Flu120+Cy80+ATG10	9.65	8.88	11	12
例7	FA	PBSC	Flu120+Cy80+ATG10	8.71	7.01	9	10
例8	DKC	PBSC	Flu160+Cy80+ATG10	17.32	13.05	10	11
例9	DKC	PBSC	Flu160+Cy80+ATG10	8.30	6.30	11	10
例10	DKC	PBSC	Flu160+Cy80+ATG10	16.03	13.84	11	12
例11	DKC	PBSC	Flu160+Cy80+ATG10	9.42	4.23	11	12
例12	DKC	PBSC	Flu160+Cy80+ATG10	13.70	8.22	11	13
例13	DBA	CBSC	Bu16+Flu160+Cy120+ATG6+TT5	0.67	0.38	13	24
例14	DBA	CBSC	Bu16+Flu160+Cy120+ATG7.5+TT10	1.29	0.15	16	28
例15	DBA	PBSC	Bu16+Cy120+ATG7.5	27.26	9.10	11	18
例16	CAMT	CBSC	Bu16+Flu120+Cy100+ATG7.5+TT10	0.56	0.15	21	30
例17	CAMT	PBSC	Bu8+Flu120+Cy100+ATG10	13.15	7.70	13	12
例18	SCN	PBSC	Bu16+Cy120+ATG7.5+TT10	10.00	4.50	15	16