Morelle Guillaume, Castelle Martin, Pinto Graziella, Breton Sylvain, Bendavid Matthieu, Boussard Charlotte, Mouy Richard, Bader-Meunier Brigitte, Semeraro Michaela, Faye Albert, Cavazzana Marina, Neven Bénédicte, Blanche Stéphane, Quartier Pierre, Moshous Despina
Pediatric Hematology-Immunology and Rheumatology Department, Necker-Enfants-Malades University Hospital, Assistance Publique Hôpitaux de Paris, 149 rue de Sèvres, 75015, Paris, France.
Pediatric Endocrinology Department, Necker-Enfants-Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
Pediatr Rheumatol Online J. 2021 Mar 12;19(1):27. doi: 10.1186/s12969-021-00523-3.
Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high.
A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs.
Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.
一些患有全身型幼年特发性关节炎（SJIA）且病情严重、难治的患者通过强化免疫抑制治疗，随后进行自体造血干细胞移植（HSCT）实现了缓解。然而，大多数病例疾病复发。最近，部分SJIA患者接受了来自 HLA 相同同胞或 HLA 匹配无关供体的异基因 HSCT。虽然大多数移植患者在停止治疗后实现了 SJIA 的持续缓解，但与手术相关的发病率很高。
一名女孩自 15 个月大起就呈现出严重的 SJIA 病程。她对甲氨蝶呤和类固醇联合抗白细胞介素（IL）-1、然后抗 IL-6、肿瘤坏死因子α抑制剂以及沙利度胺均无反应。鉴于疾病负担重且治疗相关毒性大，由于没有 HLA 匹配的供体，其母亲进行单倍体 HSCT 的指征得到了确认。该患者在 3.7 岁时接受了富含 T 细胞的骨髓移植。预处理方案包括利妥昔单抗、阿仑单抗、白消安和氟达拉滨。HSCT 后第 3 天和第 4 天使用环磷酰胺预防移植物抗宿主病，随后使用环孢素 A 和霉酚酸酯。HSCT 后的并发症包括严重感染、3 级肠道移植物抗宿主病、自身免疫性甲状腺炎和免疫性血小板减少症。HSCT 三年后，尽管持续存在需要替代治疗的甲状腺功能减退，但患儿存活且状况良好。免疫性血小板减少症已缓解。最重要的是，SJIA 完全缓解，停用了免疫抑制药物。
对于 SJIA 等炎症性疾病患者，即使使用 HLA 单倍体替代供体，异基因 HSCT 也可能是一种治疗选择。尽管这种治疗的经验有所增加，但危及生命的并发症风险限制了其仅适用于选定的严重难治性疾病患者。
