Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study

Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD. Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT. Patients' medical charts were reviewed and their data extracted using a standardised form. The outcomes assessed were allogeneic HSCT outcomes (eg, engraftment and donor chimerism, and transplant-related complications), pulmonary outcomes (eg, oxygen dependence, chest CT findings, and pulmonary function test results), and overall outcomes (eg, death, complete response, or partial response). A complete response was defined as resolution of signs of sJIA without the need for systemic immunomodulatory therapy, in addition to discontinuation of supplemental oxygen. Findings: Between Jan 18, 2018, and Oct 17, 2022, 13 patients with sJIA-LD, who were refractory to immunosuppressive treatment and who had received an average of six different treatment agents, underwent allogeneic HSCT. Ten (77%) of 13 patients were female and three (23%) were male. The median age at diagnosis of sJIA-LD was 4·8 years (IQR 2·9–14·8) and the median age at transplantation was 9·0 years (5·0–19·0). Pre-HSCT chest CT revealed characteristic sJIA-LD. Five patients required supplemental oxygen before transplantation. Patients received various reduced toxicity or intensity conditioning regimens. Grafts were from 10/10 HLA-matched (n=6) or 9/10 HLA-mismatched (n=5) unrelated donors, a 7/10 related donor (n=1), and a matched sibling (n=1). All patients engrafted. One patient had secondary graft failure and received a second transplant from a different donor. Post-transplantation complications included acute graft-versus-host disease (n=5), bacteraemia (n=8), cytomegalovirus reactivation (n=6), and post-transplantation macrophage activation syndrome (n=3). Four patients died; two from cytomegalovirus pneumonitis, one from intracranial haemorrhage, and one from progressive sJIA-LD. At a median follow-up of 16 months (IQR 6–24), all nine surviving patients had a complete response, with no active features of sJIA, no biological therapy or corticosteroid use, and no supplemental oxygen dependence. Interpretation: Allogeneic HSCT might be a valuable treatment option for patients with refractory sJIA and sJIA-LD and should be considered for children with worsening oxygen dependence or severe treatment-related morbidity. Funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR079525).