Scleroderma

Initial results from an international, investigator-initiated, open label phase 3 trial, presented at EULAR 2012, indicate that haematopoietic stem cell transplantation (HSCT) results in better long-term survival than conventional treatment for patients with poor-prognosis, early diffuse cutaneous systemic sclerosis.

The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial enrolled more than 150 patients between 2001 and 2009, and randomised participants to HSCT or IV pulse cyclophosphamide treatment. As of 1 May 2012, significantly more deaths had occurred in the conventional treatment group. Half of the deaths in the HSCT group occurred early and were deemed treatment-related, according to an independent data monitoring committee. In the conventional treatment group in contrast, none of the deaths were deemed to be treatment-related, but more deaths occurred later and most were related to progressive disease.

Speaking on behalf of European Bone Marrow Transplantation (EBMT) EULAR Scleroderma Study Group, Prof Jaap van Laar from Newcastle University, Prof Dominique Farge from Assistance Publique Hôpitaux de Paris and Prof Alan Tyndall from Basel University, explained that initial results from the trial have been very encouraging and help to identify patients who benefit from stem cell transplantation. They added that systemic sclerosis can lead to heart, lung or kidney failure and premature death, especially in patients who have the diffuse cutaneous form of the condition, where skin thickening is more generalised and involvement of vital organs more common. The ASTIS study shows that such patients may benefit from early intensive immunosuppressive treatment, they said.

The ASTIS trial was a unique collaborative project of 27 multidisciplinary teams from 10 countries conducted under the auspices of two leading organisations in the respective fields – EBMT and EULAR. The primary endpoint of the trial was event-free survival, defined as survival until death or development of major organ failure.

Systemic sclerosis is estimated to occur in 2.3 to 10 per million population. Systemic sclerosis is therefore a rare but severe autoimmune systemic connective tissue disease. Increased fibroblast activity results in abnormal growth of connective tissue which causes vascular damage and fibrosis of the skin, GI tract and other internal organs. Characteristics of systemic sclerosis include vasomotor disturbances and fibrosis with subsequent atrophy of the skin, subcutaneous tissue, muscle and internal organs, along with immunologic disturbances. Diffuse cutaneous systemic sclerosis cases make up 30 per cent of all systemic sclerosis cases and involve the upper arms, thighs and trunk. Lung fibrosis and pulmonary hypertension are important causes of mortality in these patients and there is no curative treatment available so far.

Source: Medical Independent (2012), "HSCT benefits in early diffuse cutaneous systemic sclerosis"; Original article can be found here.