Hematopoietic Stem Cell Transplantation for Systemic Sclerosis. Maria Carolina de Oliveira Ribeirão Preto Medical School University of São Paulo 2018
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1 Hematopoietic Stem Cell Transplantation for Systemic Sclerosis Maria Carolina de Oliveira Ribeirão Preto Medical School University of São Paulo 2018
2 LOCALIZED SCLERODERMA Restricted to the skin Benign Aesthetic implications SYSTEMIC SCLEROSIS Physical Limitations Poor quality of life Mortality
3 Vasculopathy Fibrosis Inflammation
4 Allanore et al. Nature Disease Primers 2015
5 Conventional Treatment Skin Methotrexate Cyclophosphamide Mycophenolate mofetil Interstitial lung Cyclophosphamide MMF GI tract Omeprazol Kidneys ACE inhibitors PAH Sidenafil Bosentan Under investigation Rituximab Tocilizumab Riociguat Nintendanib Fresolimumab
6 Despite advances in disease management, mortality of severe systemic sclerosis patients has not changed in the last 40 years. Elhai et al. Rheumatology 2012
7 Autologous Hematopoietic Stem Cell Transplantation Mobilization Cyclophosphamide 2-4g/m2 G-CSF Graft selection? Transplantation Cyclophosphamide 200mg/kg rabbit ATG G-CSF
8 Autologous Hematopoietic Stem Cell Transplantation INDICATIONS Diffuse skin involvement with worsening of the Rodnan s skin score in the past 6 months or Interstitial lung involvement with FVC or DLCO worsening >10% in 6 m
9 Autologous Hematopoietic Stem Cell Transplantation SKIN INVOLVEMENT Rodnan s score X time (years after AHSCT) Sullivan et al, BBMT 2010 Burt and Oliveira et al, Lancet 2013
10 Autologous Hematopoietic Stem Cell Transplantation 20! m PRE-TRANSPLANT 6 MONTHS 20! m SKIN INVOLVEMENT Forearm biopsies 20! m C 20! m 20! m 20! m 12 MONTHS D C 100! m 100! m 100! m 100! m 100! m 100! m Collagen change (% of Picrosirius Red staining) D * * Baseline 6 months 1 year Baseline 6 months 1 year Arruda LCM, Tese de Doutorado FMRP-USP, 2017
11 Autologous Hematopoietic Stem Cell Transplantation FVC LUNG INVOLVEMENT Pulmonary function tests DLCO Burt and Oliveira et al, Lancet 2013
12 AHSCT: randomized studies ASSIST: Autologous systemic sclerosis immune suppression trial Burt et al. Lancet 2011
13 AHSCT: randomized studies ASSIST: Autologous systemic sclerosis immune suppression trial Burt et al. Lancet 2011
14 AHSCT: randomized studies ASSIST: Autologous systemic sclerosis immune suppression trial Rodnan s score Forced Vital Capacity Burt et al. Lancet 2011
15 AHSCT: randomized studies ASTIS: Autologous stem cell transplantation vs immunosuppression van Laar et al. JAMA 2014
16 AHSCT: randomized studies ASTIS: Autologous stem cell transplantation vs immunosuppression van Laar et al. JAMA 2014
17 AHSCT: randomized studies SCOT: Scleroderma cyclophosphamide or transplantation Sullivan et al. NEJM 2018
18 AHSCT: randomized studies SCOT: Scleroderma cyclophosphamide or transplantation Sullivan et al. NEJM 2018
19 Kowal-Bielecka et al. Ann Rheum Dis 2017
20 What have we learned over the past 20 years??
21 Global survival per disease, after AHSCT RHEUMATOID ARTHRITIS MULTIPLE SCLEROSIS IDIOPATHIC JUVENILE ARTHRITIS SLE SYSTEMIC SCLEROSIS HEMATOLOGIC CYTOPENIAS SYSTEMIC SCLEROSIS Farge et al. Haematologica 2010
22 What have we learned over the past 20 years?? Patient selection - do not include advanced disease patients
23 What have we learned over the past 20 years?? Patient selection - do not include advanced disease patients Cardiac screening
24 90 transplanted patients Mortality of 6% (5 patients) 4 cardiac-related deaths Constrictive pericarditis (1) Right ventricle dysfunction (2) Left ventricle dysfunction (1) Burt, Oliveira et al. Lancet 2013
25 Pre-AHSCT Cardiac Screening Echocardiography Holter (24h EKG) Heart MRI Right sided heart catheterization Farge et al. Bone Marrow Transplant 2017
26 What have we learned over the past 20 years?? Patient selection - do not include advanced disease patients Cardiac screening Graft manipulation?
27 CD34+ graft selection p=0.41 p=0.05 p=0.04 Oliveira, Labopin et al. Bone Marrow Transplant 2016
28 What have we learned over the past 20 years?? Patient selection - do not include advanced disease patients Cardiac screening Graft manipulation? Effects on vasculopathy? Effects on gastrointestinal tract
29 Equipe Clínica Hemocentro e Centro de Terapia Celular Daniela Moraes Karla Costa Pereira Kelen Malmegrim Dimas Tadeu Covas, Juliana Elias Vanessa Leopoldo Júlia Teixeira de Azevedo, Maristela Delgado Orellana Ana Beatriz Stracieri Andreia Zombrilli Gislane Vilela, Simone Kashima, Fabiano Pieroni Marília Cirioli João Rodrigues Lima Jr Patrícia Palma Renato Cunha Ana Luísa Guimarães Marianna Vasconcelos Marco Antônio Zago, Thalita Costa Maynara Santana Gil de Santis Belinda Simões Benedito Prado Maria Carolina de Oliveira Júlio César Voltarelli (in memoriam)
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