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

Michael G Matt; Daniel Drozdov; Elisabeth Bendstrup; Mia Glerup; Ellen-Margrethe Hauge; Tania Masmas; Elvira Cannizzaro Schneider; Ulrike B Zeilhofer; Rolla F Abu-Arja; Kyla D Driest; Joseph H Oved; Karen Onel; Christen L Ebens; Deepakbabu Chellapandian; Shanmuganathan Chandrakasan; Sampath Prahalad; Johannes Roth; Susan E Prockop; Juliana Silva; Andrew H Schapiro; Christopher Towe; Sharat Chandra; Alexei Grom; Grant S Schulert; Rebecca A Marsh

doi:10.1016/S2665-9913(24)00275-3

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

Lancet Rheumatol. 2024 Dec 20:S2665-9913(24)00275-3. doi: 10.1016/S2665-9913(24)00275-3. Online ahead of print.

Authors

Michael G Matt¹, Daniel Drozdov², Elisabeth Bendstrup³, Mia Glerup⁴, Ellen-Margrethe Hauge⁵, Tania Masmas⁶, Elvira Cannizzaro Schneider⁷, Ulrike B Zeilhofer⁸, Rolla F Abu-Arja⁹, Kyla D Driest¹⁰, Joseph H Oved¹¹, Karen Onel¹², Christen L Ebens¹³, Deepakbabu Chellapandian¹⁴, Shanmuganathan Chandrakasan¹⁵, Sampath Prahalad¹⁵, Johannes Roth¹⁶, Susan E Prockop¹⁷, Juliana Silva¹⁸, Andrew H Schapiro¹⁹, Christopher Towe²⁰, Sharat Chandra²¹, Alexei Grom²², Grant S Schulert²³, Rebecca A Marsh²⁴

Affiliations

¹ Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
² Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Hematology/Oncology, Department of Pediatrics, Kantonsspital Aarau, Aarau, Switzerland; Division of Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland.
³ Center for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University Aarhus, Denmark.
⁴ Department of Child and Adolescent Medicine, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University Aarhus, Denmark.
⁵ Department of Rheumatology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University Aarhus, Denmark.
⁶ Department of Paediatrics and Adolescent Medicine, Paediatric Haematopoietic Stem Cell Transplantation and Immunodeficiency, Copenhagen University Hospital, Copenhagen, Denmark.
⁷ Division of Rheumatology Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
⁸ Division of Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland.
⁹ Pediatric Blood and Marrow Transplant Program, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA.
¹⁰ Division of Rheumatology, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA.
¹¹ Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹² Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA.
¹³ Division of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
¹⁴ Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, USA.
¹⁵ Departments of Pediatrics and Human Genetics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, USA.
¹⁶ Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, ON, Canada; Children's Hospital Lucerne and Faculty of Health Science and Medicine, University of Lucerne, Lucerne, Switzerland.
¹⁷ Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
¹⁸ Great Ormond Street Hospital for Children, London, UK.
¹⁹ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Radiology, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²⁰ Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²¹ Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²² Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²³ Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: grant.schulert@cchmc.org.
²⁴ Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Pharming Healthcare, Warren, NJ, USA. Electronic address: rebecca.marsh@cchmc.org.

PMID: 39718183
DOI: 10.1016/S2665-9913(24)00275-3

Abstract

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).