0363: 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 International Cohort
Cincinnati Children's Hospital Medical Center Cincinnati, OH, United States
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Michael Matt1, Daniel Drozdov1, Rolla Abu-Arja2, Shanmuganathan Chandrakasan3, Kyla Driest2, Elvira Cannizzaro Schneider4, Despina Moshous5, Benedicte Neven5, Karen Onel6, Sampath Prahalad7, Susan Prockop8, Pierre Quartier5, Johannes Roth9, Donna Wall10, Ulrike Zeilhofer11, Scott Canna12, Alexei Grom1, Grant Schulert1 and Rebecca Marsh1, 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Nationwide Children's Hospital, Columbus, OH, 3Emory University School of Medicine, Atlanta, GA, 4Universitaetskinderspital Zurich, Zurich, Switzerland, 5Paris Cité Université and Necker Hospital, Paris, France, 6Hospital for Special Surgery, New York, NY, 7Emory University School of Medicine, Children's Pediatric Institute, Atlanta, GA, 8Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, 9University of Ottawa, Ottawa, ON, Canada, 10The Hospital for Sick Children, Toronto, ON, Canada, 11Children's Hospital of Zurich, Zurich, Switzerland, 12Children's Hospital of Philadelphia, Philadelphia, PA
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.
M. Matt: None; D. Drozdov: None; R. Abu-Arja: None; S. Chandrakasan: Sobi, Inc, 1, 2; K. Driest: None; E. Cannizzaro Schneider: None; D. Moshous: None; B. Neven: None; K. Onel: None; S. Prahalad: None; S. Prockop: AlloVIr, 12, Support for the conduct of clinical trials through BCH, Atara, 10, 12, Support for the conduct of clinical trials through BCH, CellEvolve, 2, Jasper Therapeutics, 12, Support for the conduct of clinical trials through BCH, Pierre Fabre, 2, 6, Regeneron, 6, VOR, 2; P. Quartier: AbbVie/Abbott, 2, Amgen, 2, Novartis, 2, Pfizer, 2, Roche, 2; J. Roth: None; D. Wall: None; U. Zeilhofer: None; S. Canna: Apollo Therapeutics, 2, Novartis, 12, Site PI for industry-sponsored trial, PracticePoint CME, 6, Simcha Therapeutics, 2, Sobi, 6; A. Grom: Novartis, 2, 5, Sobi, 2, 5; G. Schulert: IpiNovyx, 5, SOBI, 2; R. Marsh: horizon, 1, sobi, 1.