J A Snowden1, A Ansari2, S Sachchithanantham2, G Jackson2, N Thompson2, A Lobo2, J Sanderson2, M Kazmi2. 1. From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK john.snowden@sth.nhs.uk. 2. From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
Abstract
BACKGROUND: Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT. DESIGN: Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres. METHODS: We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT. RESULTS: All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure. CONCLUSION: Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials.
BACKGROUND: Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT. DESIGN: Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres. METHODS: We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT. RESULTS: All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure. CONCLUSION: Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials.
Authors: Alan Graham Pockley; James O Lindsay; Gemma A Foulds; Sergio Rutella; John G Gribben; Tobias Alexander; John A Snowden Journal: Front Immunol Date: 2018-04-04 Impact factor: 7.561
Authors: Milton Artur Ruiz; Roberto Luiz Kaiser Junior; Luiz Gustavo de Quadros; Gustavo Henrique Xavier Caseiro; Aderson Francisco Oliveira; Tatiana Peña-Arciniegas; Lilian Piron-Ruiz; Fernanda Soubhia Liedtke Kaiser; Vera Lucia Oliveira Journal: Int Med Case Rep J Date: 2017-10-24
Authors: John A Snowden; Chris Hawkey; Daniel Hind; Lizzie Swaby; Katie Mellor; Richard Emsley; Laura Mandefield; Ellen Lee; Manuela Badoglio; Emmanuelle Polge; Myriam Labopin; John Gribben; A Graham Pockley; Gemma A Foulds; Alan Lobo; Simon Travis; Miles Parkes; Jack Satsangi; Diana Papaioannou; James O Lindsay Journal: BMC Gastroenterol Date: 2019-05-31 Impact factor: 3.067
Authors: B Sensi; L Siragusa; C Efrati; L Petagna; M Franceschilli; V Bellato; A Antonelli; C Arcudi; M Campanelli; S Ingallinella; A M Guida; A Divizia Journal: J Immunol Res Date: 2020-12-26 Impact factor: 4.818