Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus
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Le résumé fourni par la source
OBJECTIVE: Autologous haematopoietic cell transplantation (AHSCT) improves immunologic dysfunction in patients with SLE. However, the curative potential of this therapy remains uncertain. This study reports outcomes in SLE patients receiving a lymphodepleting, reduced intensity regimen for AHSCT in SLE. METHODS: Eight patients with SLE refractory to treatment, including i.v. cyclophosphamide (CYC), were enrolled. Five had LN and three CNS involvement as primary indications for transplant. Haematopoietic cell mobilization with CYC, G-CSF and rituximab was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of concurrent administration of CYC, fludarabine and rituximab. All immunosuppressive medications were discontinued at the start of mobilization and CS were rapidly tapered after the transplant. RESULTS: Five of eight patients achieved a complete response, including a decline in the SLEDAI to zero, which was sustained in four patients for a median of 165 months (range 138-191). One patient achieved a partial response, which was followed by relapse at month 18. Two patients with nephritis and underlying comorbidities in most organs had early deaths from infection and multiorgan failure. AHSCT resulted in profound lymphodepletion, followed by expansion of Treg cells and repopulation of naive T and B cells. Patients with a complete response showed a sustained suppression of the SLE-associated IFN-induced gene signature, marked depletion of memory and plasmablast B cells and resultant sustained elimination of anti-dsDNA antibody. CONCLUSION: Durable clinical and serologic remissions with suppression in the IFN gene signature can be achieved in refractory SLE following lymphodepleting AHSCT. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00076752.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus
- Date Crossref
- 07/12/2021
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Cancer Institute (WIA) pays non établi dans la noticeÉtablissement de santé
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Center for Cancer Research pays non établi dans la noticeStructure de recherche
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National Institutes of Health Center for Cellular Engineering pays non établi dans la noticeOrganisme public
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National Institute of Arthritis and Musculoskeletal and Skin Diseases pays non établi dans la noticeStructure de recherche
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Imperial College London pays non établi dans la noticeUniversité ou école supérieure
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Center for Clinical Research (United States) pays non établi dans la noticeEntreprise
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Ampel BioSolutions (United States) pays non établi dans la noticeEntreprise
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National Cancer Institute Center for Cancer Research pays non établi dans la noticeStructure de recherche
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Lupus Clinical Trials Unit pays non établi dans la noticeÉtablissement de santé
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Faculty of Medicine Department of Brain Sciences pays non établi dans la noticeUniversité ou école supérieure
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Rapa Therapeutics pays non établi dans la noticeInstitution
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Clinical Center Department of Radiology and Imaging Services pays non établi dans la noticeÉtablissement de santé
Cancer Institute (WIA), Center for Cancer Research et Center for Cellular Engineering — National Institutes of Health, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.