Autologous Stem-Cell Transplantation for Severe Scleroderma

Shenoy, Padmanabha; Sreenath, Sreelakshmi; Aggarwal, Amita

doi:10.1056/nejmc1801275

Cited by 13 publications

(6 citation statements)

References 8 publications

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“…Alongside, autologous HSCT has emerged as an established treatment option for some indications where effective drug therapy is not available, even in the biological era. Particularly, three randomized controlled trials (ASSIST, ASTIS and SCOT) have demonstrated the superiority of HSCT compared to monthly IV bolus of cyclophosphamide in patients with early rapidly progressive SSc in terms of event-free and overall survival, improvement of skin fibrosis, and evidence for benefits on pulmonary function [ 54 – 56 ]. SSc is now considered a standard indication for autologous HSCT [ 21 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Greco

Burman

Papa³

et al. 2021

Bone Marrow Transplant

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Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.

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Section: Methodsmentioning

confidence: 99%

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Greco

Burman

Papa³

et al. 2021

Bone Marrow Transplant

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“…The main indication for HSCT has become rapidly progressive diffuse SSc, where even in the biologic’s era, effective therapies capable of reversing tissue fibrosis and improving lung function are lacking [ 5 ]. Three randomized-controlled trials (RCTs) comparing autologous HSCT to intravenous Cy in SSc reported significant improvement in skin and broader disease-specific scores, with evidence for improvement of pulmonary function, skin fibrosis and quality-of-life [ 65 – 67 ]. A 5-year progression-free survival between 70 and 74% was reported in the multicenter European (ASTIS) and American (SCOT) trials and remained superior to monthly Cy in the control arm during the 10 years following HSCT in the ASTIS trial.…”

Section: Considerations For Hsct In Rheumatic Diseasesmentioning

confidence: 99%

“…The increased toxicity of HSCT in SSc compared to other indications was predominantly attributed to SSc-related cardiac dysfunction, especially related to pulmonary arterial hypertension, and Cy-induced cardiotoxicity. With improved screening procedures [ 68 , 69 ], as well as Cy-sparing conditioning regimens, TRM decreased from 10% in the ASTIS trial to 6% within a multicenter EBMT prospective study [ 7 ], 3% in the SCOT trial [ 67 ], and 2.4% in the CAST study [ 70 ]. Based on these data, SSc is recommended as ‘standard indication’ for autologous HSCT and endorsed by updated recommendations of the European League Against Rheumatism [ 71 ].…”

Section: Considerations For Hsct In Rheumatic Diseasesmentioning

confidence: 99%

Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Greco

2022

Bone Marrow Transplant

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Autoimmune diseases (ADs) represent a heterogenous group of complex diseases with increasing incidence in Western countries and are a major cause of morbidity. Hematopoietic stem cell transplantation (HSCT) has evolved over the last 25 years as a specific treatment for patients with severe ADs, through eradication of the pathogenic immunologic memory and profound immune renewal. HSCT for ADs is recently facing a unique developmental phase across transplant centers. This review provides a comprehensive overview of the recent evidence and developments in the area, including fundamentals of preclinical research, clinical studies in neurologic, rheumatologic and gastroenterologic diseases, which represent major indications at present, along with evidence of HSCT for rarer indications. Moreover, we describe the interwoven challenges of delivering more advanced cellular therapies, exploiting mesenchymal stem cells, regulatory T cells and potentially CAR-T cell therapies, in patients affected by ADs. Overall, we discuss past and current indications, efficacy, associated risks and benefits, and future directions of HSCT and advanced cellular therapies in the treatment of severe/refractory ADs, integrating the available literature with European Society for Blood and Marrow Transplantation (EBMT) registry data.

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“…These patients had better event-free and overall survival rates, observed after 2 years, at a cost of increased mortality. 50 Adverse effects include early mortality, increased risk of infections, and the development of new (secondary) autoimmune diseases, such as myasthenia gravis. Secondary autoimmune diseases occur in about 3.9% of HSCT cases.…”

Section: Mycophenolate Mofetil Mycophenolate Mofetil (Mmf)mentioning

confidence: 99%

Immunotherapy of systemic sclerosis

Katsiari

Simopoulou

Alexiou

et al. 2018

Human Vaccines & Immunotherapeutics

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Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, immune activation, and extensive collagen deposition. Microvasculopathy and immune activation occur very early in the disease process. Evidence from animal models and in vitro studies indicate that T-cells and B-cells activate fibroblasts to produce collagen. Traditional immunosuppressants, cyclophosphamide(CyP), methotrexate(MTX), and more recently mycophenolate mofetil(MMF), may prove more effective if used very early in the disease course. These drugs showed some benefit in skin (MTX, CyP, MMF) and lung function (CyP, MMF). Biologicals, such as intravenous immunoglobulin (IVIg), belimumab(Beli), tocilizumab(TCZ), abatacept(Aba), rituximab(RTX) and fresolimumab(Fresu) appear promising as they exhibited some benefit in skin (IVIg, Beli, TCZ, Aba, RTX, Fresu), hand function (IVIg), and joints (IVIg, TCZ, Aba). Autologous stem cell transplantation showed the best therapeutic efficacy on skin and internal organs, and looks very promising, as modification of transplantation immunosuppression is decreasing the early high mortality.

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Autologous Stem-Cell Transplantation for Severe Scleroderma

Cited by 13 publications

References 8 publications

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Immunotherapy of systemic sclerosis

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