Allogeneic hematopoietic stem cell transplantation for severe Still’s disease: a retrospective report of 3 pediatric patients

Severe forms of systemic juvenile idiopathic arthritis (sJIA), also called pediatric-onset Still's disease are associated with two major life-threatening complications: macrophage activation syndrome (MAS) and severe lung disease. Patients are usually resistant to conventional synthetic (cs) Disease-Modifying Antirheumatic Drugs (DMARDs), biologic (b) DMARDs, and targeted synthetic (ts) DMARDs. Recently, allogeneic hematopoietic stem cell transplantation (HSCT) has been performed in a small number of patients with refractory and life-threatening disease. We aimed to report outcomes and complications of allogeneic HSCT in patients with severe, refractory sJIA treated at our center. We conducted a retrospective, observational, single-center study in a tertiary pediatric immunology care center (Necker Hospital, Paris, France). We report 3 sJIA patients who underwent allogeneic HSCT at a median age of 3.5 years. All had recurrent MAS; 2 had lung disease and the HLA-DRB1*15 haplotype, associated with severe delayed hypersensitivity to IL-1/IL-6 inhibitors. Donors were matched sibling donors for the first and third patient, and matched unrelated donor for the second patient. They presented multiple post-graft complications: graft-vs-host disease, infections, thrombotic microangiopathy and severe inflammatory complications on previously affected organs, such as skin and lungs. At a median follow-up of 22 months (20-33) after transplantation, they were all in remission with full-donor chimerism and were off immunosuppressive treatment. Allogeneic HSCT can be an effective salvage therapy in patients with refractory sJIA. However the risk of post-transplant endothelial complications and severe inflammation in previously affected organs, such as joints, skin and lungs deserves particular attention.