Matt Michael G, Drozdov Daniel, Bendstrup Elisabeth, Glerup Mia, Hauge Ellen-Margrethe, Masmas Tania, Schneider Elvira Cannizzaro, Zeilhofer Ulrike B, Abu-Arja Rolla F, Driest Kyla D, Oved Joseph H, Onel Karen, Ebens Christen L, Chellapandian Deepakbabu, Chandrakasan Shanmuganathan, Prahalad Sampath, Roth Johannes, Prockop Susan E, Silva Juliana, Schapiro Andrew H, Towe Christopher, Chandra Sharat, Grom Alexei, Schulert Grant S, Marsh Rebecca A
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Hematology/Oncology, Department of Pediatrics, Kantonsspital Aarau, Aarau, Switzerland; Division of Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland.
Lancet Rheumatol. 2025 Apr;7(4):e243-e251. doi: 10.1016/S2665-9913(24)00275-3. Epub 2024 Dec 20.
Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.
This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT. Patients' medical charts were reviewed and their data extracted using a standardised form. The outcomes assessed were allogeneic HSCT outcomes (eg, engraftment and donor chimerism, and transplant-related complications), pulmonary outcomes (eg, oxygen dependence, chest CT findings, and pulmonary function test results), and overall outcomes (eg, death, complete response, or partial response). A complete response was defined as resolution of signs of sJIA without the need for systemic immunomodulatory therapy, in addition to discontinuation of supplemental oxygen.
Between Jan 18, 2018, and Oct 17, 2022, 13 patients with sJIA-LD, who were refractory to immunosuppressive treatment and who had received an average of six different treatment agents, underwent allogeneic HSCT. Ten (77%) of 13 patients were female and three (23%) were male. The median age at diagnosis of sJIA-LD was 4·8 years (IQR 2·9-14·8) and the median age at transplantation was 9·0 years (5·0-19·0). Pre-HSCT chest CT revealed characteristic sJIA-LD. Five patients required supplemental oxygen before transplantation. Patients received various reduced toxicity or intensity conditioning regimens. Grafts were from 10/10 HLA-matched (n=6) or 9/10 HLA-mismatched (n=5) unrelated donors, a 7/10 related donor (n=1), and a matched sibling (n=1). All patients engrafted. One patient had secondary graft failure and received a second transplant from a different donor. Post-transplantation complications included acute graft-versus-host disease (n=5), bacteraemia (n=8), cytomegalovirus reactivation (n=6), and post-transplantation macrophage activation syndrome (n=3). Four patients died; two from cytomegalovirus pneumonitis, one from intracranial haemorrhage, and one from progressive sJIA-LD. At a median follow-up of 16 months (IQR 6-24), all nine surviving patients had a complete response, with no active features of sJIA, no biological therapy or corticosteroid use, and no supplemental oxygen dependence.
Allogeneic HSCT might be a valuable treatment option for patients with refractory sJIA and sJIA-LD and should be considered for children with worsening oxygen dependence or severe treatment-related morbidity.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR079525).
系统性幼年特发性关节炎相关肺部疾病（sJIA-LD）是治疗难治性系统性幼年特发性关节炎（sJIA）患者的一种严重并发症。本研究的目的是评估异基因造血干细胞移植（HSCT）对一组sJIA-LD儿童患者的疗效。
这项国际回顾性队列研究在美国和欧洲的9家医院对接受异基因HSCT的sJIA-LD儿童患者进行。查阅患者的病历，并使用标准化表格提取数据。评估的结果包括异基因HSCT结果（如植入、供体嵌合率及移植相关并发症）、肺部结果（如氧依赖、胸部CT表现及肺功能测试结果）和总体结果（如死亡、完全缓解或部分缓解）。完全缓解定义为sJIA体征消失，无需全身免疫调节治疗，且停用补充氧气。
在2018年1月18日至2022年10月17日期间，13例对免疫抑制治疗难治且平均接受过六种不同治疗药物的sJIA-LD患者接受了异基因HSCT。13例患者中有10例（77%）为女性，3例（23%）为男性。sJIA-LD诊断时的中位年龄为4.8岁（IQR 2.9 - 14.8），移植时的中位年龄为9.0岁（5.0 - 19.0）。HSCT前胸部CT显示典型的sJIA-LD表现。5例患者在移植前需要补充氧气。患者接受了各种降低毒性或强度的预处理方案。移植物来自10/10 HLA匹配（n = 6）或9/10 HLA不匹配（n = 5）的无关供体、1例7/10的相关供体和1例匹配的同胞供体。所有患者均成功植入。1例患者出现继发性移植物失败，并接受了来自不同供体的第二次移植。移植后并发症包括急性移植物抗宿主病（n = 5）、菌血症（n = 8）、巨细胞病毒再激活（n = 6）和移植后巨噬细胞活化综合征（n = 3）。4例患者死亡；2例死于巨细胞病毒肺炎，1例死于颅内出血，1例死于进行性sJIA-LD。在中位随访16个月（IQR 6 - 24）时，9例存活患者均获得完全缓解，无sJIA的活动特征，无需生物治疗或使用皮质类固醇，且无补充氧气依赖。
异基因HSCT可能是难治性sJIA和sJIA-LD患者的一种有价值的治疗选择，对于氧依赖加重或有严重治疗相关发病率的儿童应予以考虑。
美国国立关节炎、肌肉骨骼和皮肤疾病研究所（R01-AR079525）
