Background/Purpose: Refractory systemic juvenile idiopathic arthritis (sJIA) in children can be complicated by repeated episodes of macrophage activation syndrome (MAS) or sJIA-related lung disease (sJIA-LD). Use of allogenic hematopoietic stem cell transplant (HSCT) has been reported in cases of refractory SJIA; however, there is limited data regarding its use in sJIA-LD. The objective of this study was to determine clinical, inflammatory, and pulmonary outcomes 6 months post-transplant in an international cohort of patients with refractory SJIA, recurrent MAS, and sJIA-LD.

Methods: Thirteen patients with refractory sJIA who underwent allogeneic HSCT from 2018-2022 were identified and analyzed. Information regarding sJIA-related treatments prior to transplant, HSCT conditioning regimens, donor HLA matching, pulmonary function tests and chest imaging, pertinent laboratory values, and transplant complications were collected using a standardized case report form. The study was completed with IRB approval from each institution.

Results: Of the 13 patients who underwent allogeneic HSCT for refractory sJIA, 10 patients had recurrent episodes of MAS, and 9 patients had progressive sJIA-LD. All patients in this study had failed treatment IL-1 and IL-6 blockade and received an average of 8 different agents (range 5-13) prior to HSCT. Many patients had received treatment with Janus Kinase inhibitors or emapalumab. The mean maximum IL-18 level prior to HSCT was 251,398 pg/mL (range 64,840-471,860 pg/mL). Most patients received grafts from 10/10 HLA-matched unrelated donors (n=6), or 9/10 HLA matched unrelated donors (n=3). Two patients received grafts from 5/10 or 7/10 HLA-mismatched related donors. Two patients received a second transplant, one for acute graft failure after 32 days and one for relapsed sJIA after one year with donor chimerism of 100%. Post-transplant complications included graft versus host disease (5 patients), bacteremia (3 patients), HHV6 reactivation, (2 patients), EBV encephalitis, CMV reactivation, and infection-triggered MAS (2 patients). One patient died 120 days after transplant due to CMV pneumonitis and multi-organ failure, and another died at day+133 with steroid dependent graft-versus-host disease and CMV pneumonitis. Six months after final transplant, 80% (10/13) of patients showed a complete clinical response, with no active features of sJIA or MAS without any biologic therapy. All patients with available post-transplant IL-18 data had normalized levels 6 months post-HSCT. Most patients (7/9) with sJIA-LD demonstrated improvement in pulmonary function, including improvements on chest CT, reduced need for supplemental oxygen, and reduced clubbing.

Conclusion: A majority of patients who underwent allogenic HSCT for refractory SJIA, recurrent MAS, or sJIA-LD showed a complete response including improvement in clinical and imaging features of lung disease. HSCT may represent a promising approach for highly refractory sJIA and its complications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/allogenic-hematopoietic-stem-cell-transplant-for-children-with-refractory-systemic-juvenile-idiopathic-arthritis-and-sjia-associated-lung-disease-6-month-post-transplant-outcomes-from-an-internationa/