EBMT

A Report from the Autoimmune Diseases Working Party (ADWP)

Overview

Figure 1
*click on images to enlarge

The use of Hematopoietic Stem Cell Transplantations (HSCT) for Autoimmune Disease has shown a continued increase over the last few years. As illustrated in Figure 1, the introduction after the year 2000 of new biological drugs resulted in a drop of the activity in certain diseases such as Rheumathoid Arthritis, whilst other forms were less affected. In particular HSCT for Multiple Sclerosis (MS) and Systemic Sclerosis (SSc) has been steadily performed with a positive trend for the former.

Diagnosis distribution is reported in Figure 1, showing a prevalence of Multiple Sclerosis over Connective Tissues Diseases, mostly due to the number of patients. Distribution of activity per countries and major centres is also reported in Figure 2 and Figure 3, respectively.

Figure 2	Figure 3

*click on images to enlarge

Prospective trials

Development and support of prospective, multicentre trials is a principle goal of the Working Party (WP). With the invaluable support of many active WP members, three prospective, randomised clinical trials have been either started or promoted in the following major diseases: Systemic Sclerosis www.astistrial.com contact Jaap M van Laar; Multiple Sclerosis www.astims.org contact Gianlugi Mancardi; and Crohn’s disease www.astic.eu contact Chris Hawkey. A fourth trial on Systemic Lupus Erythemathosus (ASTIL) is in preparation and has been submitted to the EBMT Prospective Clinical Trials Committee for review. For more information please contact the Principal Investigator Dominique Farge. The WP encourages all EBMT Members to contact the relevant specialists in their hospitals, in particular neurologists and rheumatologists, in order to inform them of existing trials, with a view to concentrating the activity within these institutional trials rather than having spontaneous, locally driven, transplant activity.

 

Paediatrics

More than 100 paediatric patients have been input to the database. Nico Wullfraat from Utrecht and Marco Rabusin from Trieste are analyzing this population of patients. Both short and long-term follow-up are particularly interesting, given the negative impact of chronic immunosuppressive treatments in this setting. The possibility of providing a prolonged steroid-free interval for these patients is identified to be clinically relevant.

 

Allogeneic

There is a growing interest towards allogeneic transplants for ADs in the case of carefully selected patients. Alois Gratwohl in Basel is running a retrospective analysis on the few patients reported to the database in order to elucidate the clinical outcome and its interaction with the immunological aspects implied in this procedure.

 

Data management

Considering the relatively small number of procedures, high quality data reported to the database is crucial in order to support the work of investigators in this field. Data management has now been transferred to the EBMT Data & Study Office in Paris.  Their current task is to update the follow-up of all registered patients and request a reference name of the physician (neurologist, rheumatologist etc.) in addition to the haematologist who is currently taking care of the patients. At present, almost 70% of the 803 patients reported have been updated, more than 200 of them having a follow-up history of longer than 5 years. Dominique Farge, from Paris, is taking care of this important task. New MED-B forms have been developed and are now being implemented for the major diagnosis; forms are available on the EBMT Website:
http://www.ebmt.org/4Registry/registry3.html

 

Biobanking

Initial, promising data have been reported on immune function after HSCT in Autoimmune Diseases(ADs) (Sun et al, 2004; Muraro et al., 2005; Farge, 2005; De Kleer, 2006). The clarification of the therapeutic role and mechanism of action of HSCT in ADs needs to be further investigated. It is crucial to collect biological specimens both before and at various time-points after HSCT to allow for future immunological investigations. Biobanking is an intrinsic part of ongoing HSCT trials, particularly in the allo setting and it is currently also carried out in collaboration with other organisations. A protocol for collection and storage of blood samples will be implemented for forthcoming trials.

 

Outreach Project

We are currently collaborating with the Outreach Committee in order to promote HSCT for ADs in countries participating in the Outreach Project. A close association at the local level with highly-experienced specialists is also needed in selected BMT Units.

 

Economic analysis

It is crucial to explore the potential health economic/cost effectiveness aspects of HSCT in autoimmune diseases. This issue is particularly relevant following the introduction of new biological drugs which has widely increased the cost of long-term treatments. John Snowden is exploring this issue in Sheffield together with the local health economic unit.

Riccardi Saccardi
Chair of the ADWP