Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.

Department of Adolescent BMT University College Hospital NHS Foundation Trust London United Kingdom

Department of BMT Great Ormond Street Hospital for Children National Health Service Foundation Trust London United Kingdom

Department of Pediatric Hematology and Oncology Teaching Hospital Motol Prague Czech Republic

Department of Rheumatology Great Ormond Street Hospital for Children NHS Foundation Trust London United Kingdom

Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center Cincinnati OH Department of Pediatrics University of Cincinnati Cincinnati OH

Great North Children's Hospital Royal Victoria Infirmary Newcastle upon Tyne United Kingdom Primary Immunodeficiency Group Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom

University College London Great Ormond Street Institute of Child Health and NIHR GOSH Biomedical Research Centre NHS Trust London United Kingdom

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