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 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
PMCID: PMC11949720 (available on 2026-04-01)
DOI: 10.1016/S2665-9913(24)00275-3

Multicenter Study

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 et al. Lancet Rheumatol. 2025 Apr.

. 2025 Apr;7(4):e243-e251.

doi: 10.1016/S2665-9913(24)00275-3. Epub 2024 Dec 20.

Authors

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
PMCID: PMC11949720 (available on 2026-04-01)
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).

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Conflict of interest statement

Declaration of interests EB received honoraria for lectures from Daiichi-Sankyo, Boehringer Ingelheim, and Novartis, and participates on an advisory board for Simbec Orion. E-MH received grants from AbbVie, Roche, Novartis, and the Novo Nordic Foundation and consulting fees from Novo Nordic, Novartis, AbbVie, Sanofi, Sobi, MSD, and USB, and is a site principal investigator for SynACT Pharma, AbbVie, Novartis, Sanofi, and Novo Nordic. JHO provided research support for Sobi, has been a member of the advisory board for Sobi, Amgen, Ensoma, and Grifols, received consulting fees from Emendo Biotherapeutics and Turn.Bio, and received honoraria as a guest lecturer from Tech Institute. SC received consulting fees from and served on an advisory board for SOBI, X4 Therapeutics, Pharming, and STAR Therapeutics and served on the scientific advisory board for CDCN, the Hyper IgM Foundation, and the Histiocyte Society. SP received honoraria from the Georgia Society of Rheumatology, was on the Macrophage Activation Syndrome adjudication committee for Novartis until 2021, and received shares of stock from Doximity. SEP receives support for the conduct of clinical trials through Boston Children's Hospital from AlloVir, Atara, and Jasper, is an inventor of intellectual property related to the development of third party viral specific T cells with all rights assigned to MSKCC, received honoraria from Pierre Fabre and Regeneron, and received consulting fees from CellEvolve and Century Therapeutics. CT received consulting fees from Boehringer Ingelheim. SC received grant funding and travel funding from the Histiocytosis Association and honoraria for lectures from the American Society of Pediatric Hematology/Oncology. AG received funding for clinical trials from Novartis and Sobi, received consulting fees from Novartis, Kiniksa, and Sobi, and receives honoraria for lectures on macrophage activation syndrome from Clearview CME. GSS received consulting fees from Boehringer Ingelheim and SOBI and research support from IpiNovyx. RAM is a part-time employee of Pharming. All other authors declare no competing interests.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials