A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.
John Moore,Peter Brooks,Sam Milliken,J. C. Biggs,David D.F. Ma,Malcolm L. Handel,Paul Cannell,Rob Will,Simon Rule,David Joske,Bob Langlands,Kerry Taylor,Joe O'Callaghan,Jeff Szer,Ian P. Wicks,Geoff McColl,Frances Passeullo,John A. Snowden +17 more
TLDR
Hemopoietic stem cell transplantation can be performed safely in patients with RA, and initial results indicate significant responses in patientsWith severe, treatment-resistant disease.Abstract:
Objective. Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.read more
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Cyclophosphamide and cancer: golden anniversary.
TL;DR: The chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders, and the development of high-dose cycloph phosphamide for BMT and the treatment of autoimmune diseases are discussed.
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Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases
Dominique Farge,Myriam Labopin,Alan Tyndall,Athanasios Fassas,Gianluigi Mancardi,Jaap Van Laar,Jian Ouyang,Tomas Kozak,John Moore,Ina Kötter,Virginie Chesnel,Alberto M. Marmont,Alois Gratwohl,Riccardo Saccardi +13 more
TL;DR: This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy.
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Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation.
John A. Snowden,Riccardo Saccardi,Matthieu Allez,Sandro Ardizzone,Raoul Arnold,Ricard Cervera,Christopher P. Denton,Christopher J. Hawkey,Myriam Labopin,G. L. Mancardi,Roland Martin,John Moore,Jakob Passweg,Christoph Peters,Marco Rabusin,Montserrat Rovira,J.M. van Laar,Dominique Farge +17 more
TL;DR: In this paper, the authors provide revised and updated guidelines for both the current application and future development of haematopoietic SCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments.
Journal ArticleDOI
Autologous stem cell transplantation for systemic lupus erythematosus.
D Jayne,Alan Tyndall +1 more
TL;DR: This registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high and the safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen.
Journal ArticleDOI
Autologous hematopoietic stem cell transplantation for autoimmune diseases.
Alois Gratwohl,Jakob Passweg,Chiara Bocelli-Tyndall,A Fassas,J.M. van Laar,Dominique Farge,M Andolina,Renate Arnold,Enric Carreras,Jürgen Finke,Ina Kötter,Tomas Kozak,I. Lisukov,Bob Löwenberg,Alberto M. Marmont,John Moore,Riccardo Saccardi,John A. Snowden,F.H.J. van den Hoogen,NM Wulffraat,X. Zhao,Alan Tyndall +21 more
TL;DR: Data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.
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