Sustained Remission After Haploidentical Bone Marrow Transplantation in a Child With Refractory Systemic Juvenile Idiopathic Arthritis

Abstract

Background: 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.Case report: A girl presented SJIA since the age of 15 months with a severe disease course. 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. Therefore, allogenic HSCT was considered. In the absence of any possible HLA matched donor, a multidisciplinary team carefully assessed risks and benefits of a transplant procedure with an alternative donor. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated. 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.Conclusion: 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.

Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

“…43 Sustained CR was also reached in the first child transplanted with a haploidentical donor for severe JIA. 54 However, allogeneic transplant was associated with significant TRM (13%) and clinically relevant treatment-related toxicity as acute GvHD grade II-IV (19%), infections (56%) and auto-or alloimmune cytopenia (25%), concluding that this procedure should be evaluated in controlled trials. 43,55 Childhood-onset systemic lupus erythematosus (cSLE) is a rare chronic inflammatory disease affecting multiple systems and occurring before the age of 18 years.…”

“…Allogeneic HSCT with an HLA‐identical sibling or an unrelated HLA‐matched unrelated donor has been successfully performed in a paediatric cohort of 16 patients with JIA, 11 of which (69%) achieved stable CR 43 . Sustained CR was also reached in the first child transplanted with a haploidentical donor for severe JIA 54 . However, allogeneic transplant was associated with significant TRM (13%) and clinically relevant treatment‐related toxicity as acute GvHD grade II–IV (19%), infections (56%) and auto‐ or alloimmune cytopenia (25%), concluding that this procedure should be evaluated in controlled trials 43,55 …”