Outcome of Non-hematological Autoimmunity After Hematopoietic Cell Transplantation in Children with Primary Immunodeficiency,Journal of Clinical Immunology

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Outcome of Non-hematological Autoimmunity After Hematopoietic Cell Transplantation in Children with Primary Immunodeficiency
Journal of Clinical Immunology ( IF 7.2 ) Pub Date : 2020-11-03 , DOI: 10.1007/s10875-020-00895-3
Su Han Lum _{1,

2} , Reem Elfeky ₃ , Federica R Achini _{2,

4} , Adriana Margarit-Soler ₅ , Bianca Cinicola ₃ , Inigo Perez-Heras ₁ , Zohreh Nademi _{1,

6} , Terry Flood ₁ , Tim Cheetham _{6,

7} , Austen Worth ₃ , Waseem Qasim ₃ , Rakesh Amin ₈ , Kanchan Rao ₅ , Robert Chiesa ₅ , Robbert G M Bredius ₂ , Persis Amrolia ₅ , Mario Abinun ₆ , Sophie Hambleton _{1,

6} , Paul Veys ₅ , Andrew R Gennery _{1,

6} , Arjan Lankester ₂ , Mary Slatter _{1,

6}

Affiliation

Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Clinical Resource Building, Floor 4, Block 2, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.
Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Division of Pediatric Stem Cell Transplantation and Children's Research Center (CRC), University Children's Hospital of Zurich, Zurich, Switzerland.
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Department of Paediatric Endocrinology, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK.
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Purpose

Knowledge of post-hematopoietic cell transplantation (HCT) non-hematological autoimmune disease (AD) is far from satisfactory.

Method

This multicenter retrospective study focuses on incidence, risk factors, and outcomes of post-HCT AD in 596 children with primary immunodeficiency (PID) who were transplanted from 2009 to 2018.

Results

The indications of HCT were severe combined immunodeficiency (SCID, n = 158, 27%) and non-SCID PID (n = 438, 73%). The median age at HCT was 2.3 years (range, 0.04 to 18.3 years). The 5-year overall survival for the entire cohort was 79% (95% cumulative incidence (CIN), 74–83%). The median follow-up of surviving patients was 4.3 years (0.08 to 14.7 years). The CIN of post-HCT AD was 3% (2–5%) at 1 year post-HCT, 7% (5–11%) at 5 years post-HCT, and 11% (7–17%) at 8 years post-HCT. The median onset of post-HCT AD was 2.2 years (0.12 to 9.6 years). Autoimmune thyroid disorder (n = 19, 62%) was the most common post-HCT AD, followed by neuromuscular disorders (n = 7, 22%) and rheumatological manifestations (n = 5, 16%). All patients but one required treatment for post-HCT AD. After multivariate analysis, age at transplant (p = 0.01) and T cell–depleted graft (p < 0.001) were significant predictors of post-HCT AD. None of the T cell–depleted graft recipients developed post-HCT AD. Patients with a lower CD3+ count at 6 months post-HCT had a significant higher incidence of post-HCT AD compared to disease controls. Graft-versus-host disease, viral infection, and donor chimerism had no association with post-HCT AD.

Conclusion

Post-HCT AD occurred in 11% at 8 years post-HCT and its occurrence was associated with older age at HCT and unmanipulated graft.

中文翻译：

原发性免疫缺陷儿童造血细胞移植后非血液学自身免疫的结果

目的

造血细胞移植后 (HCT) 非血液自身免疫性疾病 (AD) 的知识远不能令人满意。

方法

这项多中心回顾性研究侧重于 2009 年至 2018 年移植的 596 名原发性免疫缺陷 (PID) 儿童的 HCT 后 AD 的发生率、危险因素和结果。

结果

HCT的适应症是重度联合免疫缺陷（SCID，n = 158, 27%）和非SCID PID（n = 438, 73%）。HCT 的中位年龄为 2.3 岁（范围为 0.04 至 18.3 岁）。整个队列的 5 年总生存率为 79%（95% 累积发病率 (CIN)，74-83%）。存活患者的中位随访时间为 4.3 年（0.08 至 14.7 年）。HCT 后 AD 的 CIN 在 HCT 后 1 年为 3% (2-5%)，在 HCT 后 5 年为 7% (5-11%)，在 8 年为 11% (7-17%) HCT 后。HCT 后 AD 的中位发病时间为 2.2 年（0.12 至 9.6 年）。自身免疫性甲状腺疾病 ( n = 19, 62%) 是 HCT 后最常见的 AD，其次是神经肌肉疾病 ( n = 7, 22%) 和风湿病表现 ( n = 5, 16%)。除一名患者外，所有患者都需要接受 HCT 后 AD 治疗。多变量分析后，移植年龄 ( p = 0.01) 和 T 细胞耗尽的移植物 ( p < 0.001) 是 HCT 后 AD 的重要预测因子。没有一个 T 细胞耗尽的移植受者在 HCT 后出现 AD。与疾病对照组相比，HCT 后 6 个月 CD3+ 计数较低的患者发生 HCT 后 AD 的发生率显着升高。移植物抗宿主病、病毒感染和供体嵌合与 HCT 后 AD 无关。