Department of Paediatric Immunology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Mol Immunol. 2009 Nov;47(1):46-51. doi: 10.1016/j.molimm.2008.12.029. Epub 2009 Feb 8.
As part of collaborative multi-centre study started in 2000, 7 children in the UK fulfilled the inclusion criteria for treatment with autologous T cell depleted (TCD) haematopoietic stem cell transplantation (HSCT) for severe juvenile idiopathic arthritis (JIA). Here we report on the outcome and transplant-related complications.
The initial, often dramatic clinical response in all patients was followed in 4 with sustained benefit, including the withdrawal of immunosuppressive and anti-inflammatory treatment, significant catch-up growth and immense improvement of the quality of life during 5-8 years long follow-up. Two patients relapsed within 1-12 months, and one died 4 months post transplant.
Adenovirus reactivation with dissemination was lethal in one patient, whilst Epstein-Barr (EBV) and cytomegalovirus (CMV) reactivation-driven haemophagocytic syndrome responded to antiviral and immunomodulatory treatment in 2 patients. Both the conditioning and the T cell depletion of the graft, leading to severe immunosuppression and prolonged immune system function reconstitution, are the main predisposing factors for potentially life-threatening transplant-related complications.
Autologous TCD HSCT for children with severe JIA results in two-phase response. The initial remission seen in all patients is due to immunosuppressive conditioning. This is followed by sustained drug-free remission in over 50% of patients, which is due to 'immunomodulatory' effects of TCD HSCT. The procedure carries a significant morbidity and mortality risk. However, this risk should be balanced against the risks of life-threatening infections occurring in this very selective group of patients on long-term and combined immunosuppressive and anti-inflammatory therapies. How to correctly identify and appropriately assess the patients in need for autologous TCD HSCT, particularly in relation to optimizing the timing for the procedure in regards to the newly available therapies with different biologic response modifiers, are some of the most important questions awaiting answers from this on-going study.
作为 2000 年开始的合作多中心研究的一部分，英国的 7 名儿童符合接受自体 T 细胞耗竭（TCD）造血干细胞移植（HSCT）治疗严重幼年特发性关节炎（JIA）的纳入标准。在此，我们报告其结果和与移植相关的并发症。
所有患者最初经常出现明显的临床缓解，其中 4 例持续受益，包括停止免疫抑制和抗炎治疗、显著追赶生长和在 5-8 年的长期随访中生活质量的巨大改善。2 例患者在 1-12 个月内复发，1 例患者在移植后 4 个月死亡。
1 例患者腺病毒再激活伴播散是致命的，而 2 例患者的 EBV 和 CMV 再激活引起噬血细胞综合征对抗病毒和免疫调节治疗有反应。供体的调理和 T 细胞耗竭导致严重的免疫抑制和延长的免疫系统功能重建，是潜在危及生命的与移植相关的并发症的主要诱发因素。
自体 TCD HSCT 治疗严重 JIA 的儿童可引起两阶段反应。所有患者均可见初始缓解，这是由于免疫抑制调理所致。随后，超过 50%的患者出现持续无药物缓解，这是由于 TCD HSCT 的“免疫调节”作用所致。该过程具有显著的发病率和死亡率风险。然而，与长期联合免疫抑制和抗炎治疗的这一非常选择性患者群体中发生危及生命的感染的风险相比，这种风险应该平衡。如何正确识别和适当评估需要自体 TCD HSCT 的患者，特别是在与新的生物反应调节剂相关的不同治疗方法优化该程序的时机方面，是该正在进行的研究中需要回答的一些最重要的问题。
