Upfront stem cell transplantation versus rescue stem cell transplantation in early diffuse cutaneous systemic sclerosis

13 van de 
patients are included in the study


This is the official website of the UPSIDE trial

The aim of this international randomised trial is to determine the optimal treatment strategy in patients with early diffuse cutaneous systemic sclerosis (dcSSc). The effectiveness of autologous stem cell transplantation (SCT) will be compared with immunosuppressive therapies (including cyclophosphamide and mycophenolate mofetil (MMF).

We investigate the impact of these two treatment strategies on i.e. skin and internal organ involvement, safety, daily functioning, quality of life.

This trial is initiated and coordinated by the University Medical Centre Utrecht in the Netherlands. This website provides information and news about the trial for patients, health care professionals and investigators.

Dit onderzoek wordt gesteund door:



Background information

Diffuse cutaneous systemic sclerosis (dcSSc) is a progressive, severe systemic autoimmune disease which is characterised by inflammation and fibrosis of the connective tissue, leading to skin thickening, organ damage, limited daily functioning and premature death.

Unfortunately systemic sclerosis is incurable. However, there are treatments to stop or slow down disease progression by suppressing the immune system: cyclophosphamide (CYC), mycophenolate mofetil (MMF) or methotrexate (MTX), or resetting the immune system (stem cell transplantation).

Since 20 years, autologous stem cell transplantation (SCT) is used to treat systemic sclerosis. Two previous trials demonstrated that SCT was more effective compared to intravenous CYC with regard to skin and lung involvement and quality of life. However, SCT was also associated with a higher risk of severe, treatment-related complications. Because of the latter, SCT is mostly done in case other treatments fail. On the other hand, upfront SCT, early in the course of the disease, could let to less complications and even be more effective, instead of later on in advanced disease. Furthermore, when immunsuppressive medication does not work, severe organ damage due to disease progression could occur, leading to exclusion from SCT as a rescue treatment.

It is currently not known what the best treatment strategy in early dcSSc is, and what the optimal timing of SCT is. The UPSIDE trial investigates two treatment strategies in order to answer the question: Upfront SCT or SCT when other treatments fail?

Study design

In total, 15 centres in Europe participate in the UPSIDE trial. Treatment is allocated by randomisation, this means that a computer will decide independently and randomly which treatment strategy will be used. Both the patient and the investigator know which treatment is given (this is called: an open-label trial).

Adults with disease duration less than 2 years with diffuse skin involvement and/or organ involvement can participate in the trial.

Patients will randomise for study arm A: upfront SCT or

study arm B: immunosuppressive therapy first (1 year monthly iv cyclophosphamide followed by 1 year of MMF). If needed SCT can be provided in case of progression despite immunosuppressive therapies. 

After completion of the trial we will compare outcomes in both study arms. Outcomes that will be evaluated are: progression free survival, changes in skin and lung involvement, treatment related complications, changes in microcirculation (nail fold capillaroscopy), changes in cardiac function, quality of life, daily functioning, sexual health, hand mobility, fatigue and work.
Results of this study will provide more insight in the optimal treatment strategy and will support patients and physicians in making treatment decisions.
Er zijn nog 107 plaasten beschikbaar
Places available 89%

Inclusions per centre

Who can participate?

For this trial we are looking for adults with early dcSSc with:

A screening take place prior to inclusion. This is done to determine whether you could safely undergo the treatments provided in the study. This is in line with screening done in routine clinical practise and includes: blood tests, urine test, lung function test, cardiac echo, ECG, 24-hour holter, cardiac MR and right heart catheterisation.

What happens when you participate in the trial?

In this trial you are randomly allocated to one of the two abovementioned treatment strategies. Randomisation means that the participant, investigators and physicians cannot influence the treatment choice.

We do not use any experimental drugs in this trial. All treatments are already used in usual care in systemic sclerosis. Half of the participants will be treated with upfront stem cell transplantation (SCT), the other half will be treated with monthly infusions with cyclophosphamide for 12 months followed by mycophenolate mofetil for another 12 months. Importantly, in case of progression patients can get a rescue SCT.

Participation takes 5 years. Medical data will be collected during this period. Also you will be invited to complete questionnaires and we will ask you to participate in several sub-studies (i.e. additional collection of blood). In these sub-studies we investigate the mechanism of action of therapies and will aim to identify predictors for response.

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Ut elit tellus, luctus nec ullamcorper mattis, pulvinar dapibus leo.




Aan de UPSIDE studie zijn een aantal deelstudies gekoppeld die aanvullend andere aspecten van systemische sclerose en/of de behandelingen onderzoeken. 

Als u deelneemt aan de UPSIDE studie kan u ook meedoen aan de deelstudies. Hieronder vindt u informatie over de verschillende deelstudies.


Study diagram


Questions about participation or referral can be addressed to::

General comments or questions

Participating centres

UMC Utrecht, The Netherlands

Leiden UMCU, The Netherlands

Amsterdam UMC, The Netherlands

Skåne University Hospital, Lund, Sverige

Karolinska Institute, Stockholm, Sverige

Basel Universitätsspital, Schweiz



Ospedale San Raffaele, Milano, Italia

Universitatsklinikum Wurzburg, Deutschland

Universitatsklinikum Tuebingen, Deutschland