单倍体造血干细胞移植治疗伴LRBA缺陷的ALPS样表型1例报告

doi:10.12372/jcp.2025.24e0394

摘要/Abstract

摘要：

患儿男，1个月24天，诊断为免疫性血小板减少症（ITP）和自身免疫性溶血性贫血（AIHA）。全外显子基因测序显示LRBA复合杂合突变，诊断为LRBA缺陷伴自身免疫性淋巴细胞增生性综合征（ALPS）样表型。在皮质类固醇、新生儿样换血、利妥昔单抗、西罗莫司等治疗后ALPS样表型症状不能改善，且伴有肺部感染、巨细胞病毒血症，于出生后3个月行父亲单纯骨髓来源的单倍体造血干细胞移植（HSCT）。移植后，患儿血小板和粒细胞成功植入，感染得到控制，未出现严重并发症。移植后3个月患儿经历Ⅱ级皮肤移植物抗宿主病（GVHD），经治疗后完全缓解。目前患儿移植后8月余，健康存活，免疫功能恢复正常，ALPS样表型未复发。本文回顾性分析1例小年龄的LRBA缺陷伴ALPS样表型患儿，评估其接受携带突变的父亲骨髓来源造血干细胞治疗的有效性和安全性。研究表明，对于一线治疗无效的患儿，应尽早行HSCT。在无全相合供体时，单倍体供体和骨髓来源干细胞是可行的选择，可促进植入，降低GVHD和感染风险，提高移植成功率。未来需进一步研究优化治疗方案，以改善预后。

关键词: LRBA缺陷, 自身免疫性淋巴细胞增生性综合征样, 骨髓移植, 儿童

Abstract:

A male infant, aged 1 month and 24 days, was diagnosed with immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Whole-exome gene sequencing revealed compound heterozygous mutations of LRBA, confirming a diagnosis of LRBA deficiency with an ALPS-like phenotype. Despite treatments with corticosteroids, neonatal-like exchange transfusions, rituximab, and sirolimus, the ALPS-like symptoms persisted and were complicated by pulmonary infection and cytomegalovirus viremia. At 3 months of age, the patient underwent haploidentical hematopoietic stem cell transplantation (HSCT) using bone marrow from his father. Post-transplantation, successful engraftment of platelets and granulocytes was achieved, infections were controlled, and no severe complications occurred. Three months after transplantation, the infant developed grade Ⅱ skin graft-versus-host disease (GVHD), which resolved completely following treatment. Currently, more than 8 months after transplantation, the patient remains healthy with normalized immune function and no recurrence of the ALPS-like phenotype. This article retrospectively analyzed a case of a young patient with LRBA deficiency and an ALPS-like phenotype, evaluating the efficacy and safety of HSCT using bone marrow-derived hematopoietic stem cells from a haploidentical father. The study indicates that for children unresponsive to first-line treatments, HSCT should be considered as early as possible. In the absence of a fully matched donor, haploidentical donors and bone marrow-derived stem cells represent viable options that may enhance engraftment, reduce GVHD and infection risks, and improve transplantation outcomes. Further studies are required to optimize the treatment protocol and improve prognosis.

Key words: LRBA deficiency, ALPS-like, bone marrow transplantation, child

王庆伟, 周敏, 程生钦, 肖佩芳, 卢俊, 李捷, 胡绍燕. 单倍体造血干细胞移植治疗伴LRBA缺陷的ALPS样表型1例报告[J]. 临床儿科杂志, 2025, 43(5): 367-370.

WANG Qingwei, ZHOU Min, CHENG Shengqin, XIAO Peifang, LU Jun, LI Jie, HU Shaoyan. The treatment of ALPS-like with LRBA deficiency by haploid hematopoietic stem cell transplantation: a case report[J]. Journal of Clinical Pediatrics, 2025, 43(5): 367-370.

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